| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
IMMUNOLOGY, HEALTH, AND DISEASE |
* Section of Immunology, Adaptation Physiology Group, and Cell Biology and Immunology Group, Department of Animal Sciences, Wageningen University, Marijkeweg 40, 6709 PG Wageningen, the Netherlands
1 Corresponding author: Henk.Parmentier{at}wur.nl
 |
ABSTRACT |
|---|
 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
Key Words: pathogen-associated molecular pattern • modulation • vaccine • intratracheal • airborne
|
INTRODUCTION |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
0.1 ng/m3) have been found on chicken farms (Douwes, 1998). The Dutch Health Council has advised a limit of 50 EU/m3 for endotoxin levels in a work environment for humans (Douwes, 1998; Dusseldorp et al., 2004), which thus far is less than is found in chicken or pig farms. Exposure to bacteria and bacterial cell wall components has been suggested to be causally related to respiratory health problems of humans (Douwes, 1998; Douwes et al., 2004) and to the reported increase in respiratory diseases of poultry (Appleby et al., 2004). Lipopolysaccharide, being proinflammatory, has been associated with airway diseases of animals (Vernooy et al., 2002), also causing clinical symptoms such as fever, anorexia, and decreased growth in layers, all characteristics of acute phase-like responses (Barnes et al., 2002). Furthermore, increased pulmonary arterial pressure in broilers (Wideman et al., 2004; Chapman et al., 2005), decreased respiratory capacity and death (Rocksen et al., 2004), and chronic airway inflammation in mice after repeated intratracheal (i.t.) administration of LPS (Vernooy et al., 2002) have been reported. Lipoteichoic acid also has immunomodulating features by inducing the activation of nuclear factor-
B, which results in activation of inducible NO synthase and NO production in macrophages (Kao et al., 2005). The production of large amounts of NOx by inducible NO synthase has been implicated in the genesis of septic and cytokine-induced circulatory shock (Kao et al., 2005). 1,3 ß-Glucan has been shown to stimulate inflammatory cytokine production and activation of complement without Ig (Frasnelli et al., 2005). Sjöstrand and Rylander (1997) have suggested that exposure to molds could deteriorate an existing inflammation in the lungs induced by inflammatory agents such as smoke, air pollution, or microbial infection. Furthermore, i.t. instillation of BGL (from baker’s yeast) has induced pulmonary inflammation in rats (Young et al., 2001). On the other hand, in the presence of a strong stimulus, BGL can down-regulate harmful immune hyperactivity (Pelizon et al., 2003). Previously, we described immunomodulating activities of LPS and LTA when administered intravenously (i.v.) shortly prior to primary and secondary subcutaneous immunization with model antigens (Parmentier et al., 2004; Maldonado et al., 2005). In short, LTA enhanced, whereas LPS depressed, specific antibody (Ab) responses to model T-cell-dependent antigens, such as keyhole limpet hemocyanin, BSA, and rabbit gamma globulin. This result suggests skewing of the immune response of chickens to either T-helper-1- (TH-1) or T-helper-2 (TH-2)-like immune reactivity, via binding of the PAMP to Toll like receptors (TLR) present on dendritic cells, as has been described in mammals (Kapsenberg, 2003). This may result in the release of proinflammatory cytokines interleukin (IL)-12 or, alternatively, differentiation of the immune response toward the TH-2 route (Werling and Jungi, 2002). In mice, LPS has been found to react via TLR-4 (Calkins et al., 2002; Werling and Jungi, 2002; Talreja et al., 2004; Kao et al., 2005). Lipoteichoic acid may activate cells via TLR-2 (Werling and Jungi, 2002; Lee et al., 2004; Talreja et al., 2004), and BGL has been found to react via TLR-2 and probably other receptors (Frasnelli et al., 2005).
In the present study, we evaluated the effects of a likely more natural route of challenge with PAMP (the respiratory tract of birds) with LPS, LTA, or BGL on primary and secondary Ab responses to the model antigen human serum albumin (HuSA), and Ab titers due to routine vaccination against infectious bursal disease (IBD, Gumboro) virus and infectious bronchitis (IB) virus. Lipopolysaccharide, LTA, or BGL was administered on 5 consecutive days prior to primary and secondary subcutaneous immunization with HuSA to mimic a (semi)chronic condition. Modulation of specific Ab responses of poultry after respiratory challenge with PAMP may have important consequences for health management procedures, including application of vaccines, immune-mediated disease resistance, and production or growth of poultry.
|
MATERIALS AND METHODS |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
Reagents
Escherichia coli-derived LPS (L2880, serotype O55:B5), Staphylococcus aureus-derived LTA (L2515), BGL derived from Saccharomyces cerevisiae (Zymosan A, Z-4250), and HuSA (Lot 8763) were from Sigma-Aldrich Inc. (St. Louis, MO). Heat-inactivated IB and IBD virus culture suspensions were kindly provided by Winfried Degen (Intervet BV, Boxmeer, the Netherlands).
Experimental Design
At 9 wk of age (i.e., d 0 of the experiment) and 3 mo thereafter, chicks received i.t. either 0.5 mg of LPS, 0.5 mg of LTA, or 0.5 mg of BGL dissolved in 0.5 mL of PBS, pH 7.2, or only 0.5 mL of PBS (control group). Challenges were performed by placing a 1.2 x 60 mm blunted anal cannula (InstruVet, Cuijk, the Netherlands), on a 1-mL syringe, gently into the trachea of the chick. The birds received the same treatment for 5 consecutive days. On the fifth day of treatment of the primary period and 3 mo later, all birds were immunized subcutaneously with 1 mg of HuSA dissolved in 1 mL of PBS. Eight days prior to the first immunization with HuSA and at 3, 6, 13, 20, and 28 d after primary immunization, 1 mL of blood was taken from the wing vein of all birds. Similarly, blood was taken from all birds at 15 d prior to and at d 3, 7, 10, and 14 after secondary immunization with HuSA (i.e., at 76, 94, 98, 101, 105 d after primary immunization). Serum was stored at –20°C until use. Body weights of the chickens were recorded at various times, from which their growth was calculated.
Humoral Immune Response to HuSA and PAMP
Total Ab titers to HuSA, LPS, LTA, and BGL in serum from all individual birds were determined by ELISA at d –8, 3, 6, 13, 20, and 28 after primary immunization, and at d –15, 3, 7, 10, and 14 after secondary immunization with HuSA. Briefly, 96-well plates were coated with 100 µL/well of either 4 µg/mL of HuSA, 4 µg/mL of LPS, or 10 µg/mL of LTA. 1,3 ß-Glucan (40 µg/mL) was coated as described previously (Ma et al., 2004). After subsequent washing with H2O containing 0.05% Tween, the plates were incubated with serial dilutions of serum in 1% newborn calf serum containing PBS. Controls consisted of similar serial dilutions with pooled serum from birds that had not been immunized with HuSA (negative control) and pooled serum from all chickens immunized with HuSA obtained 14 d postinfection (positive control) present on every plate. Binding of total chicken Ab to HuSA, LPS, LTA, and BGL was detected using 1:20,000 diluted rabbit antichicken IgGH+L coupled to peroxidase (Nordic). In addition, IgM, IgA, and IgG antibodies binding to HuSA were determined at all times. After incubation with serial dilutions of serum, plates were incubated with 1:20,000 diluted goat antichicken IgM coupled to peroxidase, goat antichicken IgGFc coupled to peroxidase, or goat antichicken IgA coupled to peroxidase, all from ITK Diagnostics (Uithoorn, the Netherlands). After washing, tetramethylbenzidine and 0.05% H2O2 were added and incubated for 10 min at room temperature. The reaction was stopped with H2SO4. Extinctions were measured with a Multiscan instrument (Labsystems, Helsinki, Finland) at a wavelength of 450 nm. Titers were expressed as log2 values of the dilutions that gave an extinction closest to 50% of Emax, where Emax represents the highest mean extinction of a standard positive (pooled) serum present on every microtiter plate.
Humoral Immune Response to IBD and IB Vaccines
Total Ab titers to IBD and IB vaccines in the serum from all birds were determined by ELISA at d –8, 3, 6, 13, 20, and 28 after primary immunization with HuSA, and at d –15, 3, 7, 10, and 14 after secondary immunization with HuSA. Briefly, 96-well plates were coated with either a 1:400 diluted antigen prepared from 1,000 units of heat-inactivated IBD and IB virus culture suspensions, respectively. After subsequent washing with H2O containing 0.05% Tween, the plates were incubated with serial dilutions of serum in 1% newborn calf serum containing PBS. A pooled serum from all birds obtained at d 27 postimmunization with HuSA (i.e., approximately 13 wk of age) served as the reference serum to calculate titers. Binding of total chicken Ab to the IBD and IB vaccines was detected using 1:20,000 diluted rabbit antichicken IgGH+L coupled to peroxidase. Subsequent procedures were as described above.
Statistical Analysis
Primary and secondary total Ab responses to HuSA, LPS, LTA, and BGL; primary and secondary isotype Ab (IgM, IgA, and IgG) responses to HuSA; total Ab titers to IBD and IB vaccines; and BW (gain) were analyzed by 2-way ANOVA for the effects of treatment (PAMP administration), time, and their interactions using the repeated measures procedure, with the bird nested within (PAMP) treatment option. In addition, PAMP treatment effects per sample time point were analyzed by 1-way ANOVA. Body weight gain (growth) per sample time point was analyzed by 1-way ANOVA for the effect of PAMP treatment. All analyses were done according to SAS Institute (1990) procedures. Mean differences between (PAMP) treatments were tested with Bonferroni’s test.
|
RESULTS |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
shows the kinetics of the total Ab titers (Figure 1, panel A) and the isotypes IgM (Figure 1, panel B), IgG (Figure 1, panel C), and IgA (Figure 1, panel D) to HuSA of birds i.t. challenged with LPS, LTA, BGL, or PBS. The highest titers of all isotypes were found at 6 d after primary immunization and at 7 (LTA-treated birds) or 10 d after secondary immunization with HuSA (birds from the other treatment groups).
|
; P < 0.05). There were neither significant (PAMP) treatment effects nor contrasts between the 4 treatment groups (Table 1). In addition, at separate sample time points no significant treatment effects were found for total and all isotype Ab titers apart from IgA. Lipoteichoic acid significantly enhanced primary responses to HuSA as compared with PBS (Figure 1
, panel D).
|
; P < 0.05). The highest average titers of total Ab were found in the LTA-challenged birds, which differed significantly from the BGL- and PBS- (control) treated birds. Although not significant (P < 0.1), LTA also enhanced the average IgA responses to HuSA. Lipoteichoic acid significantly enhanced secondary IgG responses to HuSA as compared with BGL- and PBS-(control) treated birds (Table 1; P < 0.05). At d 10 postimmunization, LTA significantly enhanced IgM responses to HuSA (Figure 1, panel B). At d 7, 10, and 14 postsecondary immunization with HuSA, LTA treatment significantly enhanced total Ab titers (Figure 1, panel A), and at d 7, 10, and 14 postsecondary immunization LTA significantly enhanced IgG Ab titers to HuSA (Figure 1, panel C) as compared with the PBS- (control) treated group (P < 0.05). Similarly, LPS significantly enhanced total Ab titers at d 3 and 10 (Figure 1, panel A) and IgG Ab titers to HuSA at d 3 postsecondary immunization with HuSA (Figure 1, panel C) as compared with PBS-treated birds. No time x treatment interaction was found for the average isotype responses. At d 7 postsecondary immunization, LTA significantly enhanced IgA Ab responses to HuSA as compared with the PBS group (Figure 1, panel D). Birds challenged with LTA had significantly higher titers at d 7 postsecondary immunization, whereas the other groups peaked at d 10 postsecondary immunization.
Ab Responses to PAMP
Mean average total Ab responses to LPS, LTA, and BGL in birds i.t. pretreated with PAMP on 5 consecutive days prior to either primary or secondary immunization with HuSA are shown in Table 2. Average total Ab responses to PAMP after primary and secondary treatment were not significantly affected by treatment. However, Ab titers binding LPS were significantly enhanced as compared with the PBS (control) group at d 3 and 6 after primary challenge (Figure 2). At d 3 after secondary challenge with HuSA, Ab titers binding LPS were significantly enhanced as compared with the PBS (control) group, whereas at all sample moments Ab titers binding LPS were significantly lower in the birds challenged twice with LTA as compared with the LPS-treated birds.
|
|
and 4 show the kinetics of the total Ab titers to IB and IBD, respectively. Mean average total Ab titers to IBD and IB in birds i.t. treated with PAMP on 5 consecutive days prior to either primary or secondary immunization with HuSA are shown in Table 3. Average total Ab titers to the vaccines after the primary and secondary treatments with PAMP were not significantly affected by treatment. However, Ab titers binding IBD were significantly enhanced in the LTA group (P < 0.05) as compared with the BGL-treated and the PBS- (control) treated groups. The LTA-treated birds showed significantly enhanced Ab titers to IBD at d 13 and 28 after primary challenge with HuSA and at d 0 after secondary challenge with HuSA as compared with PBS-treated birds. In LPS-treated birds, a significantly enhanced anti-IBD Ab titer was found at d 7 postimmunization with HuSA as compared with PBS- (control) treated birds. The anti-IB Ab titer was significantly enhanced in LTA-treated birds as compared with PBS-treated birds and in LPS-treated birds on d 3 after secondary immunization with HuSA.
|
|
|
). Overall, no significant treatment effects were found in time. However, a significant reduction in average BW gain was found at 1 d after the first i.t. challenge with LPS (–16 g) as compared with the LTA (+9 g), BGL (+18 g), and PBS (+15 g) treatments (P < 0.001) during the primary treatment period. At 1 d after the second i.t. challenge, both the LPS (–39 g) and BGL (–36 g) treatments, and to a minor extent the LTA (–15 g) treatment, induced a significant reduction in BW gain as compared with the PBS treatment (–4 g; P < 0.05). All birds treated with PAMP had lower BW than PBS-challenged birds. Lipopolysaccharide-treated and BGL-treated birds showed lower BW than LTA-challenged birds.
|
|
DISCUSSION |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
We studied the effect of (repeated) i.t. challenge of growing chickens with PAMP on primary and secondary Ab responses to the model T-cell-dependent antigen HuSA as a model for respiratory tract challenge with PAMP and the consequences for Ab responses to HuSA and 2 vaccines. Lipopolysaccharide, LTA, and BGL were chosen as representative PAMP from gram-negative or gram-positive bacteria, molds, and plants. Human serum albumin was chosen as a (PAMP-free) model antigen to prevent possible interference with obligatory vaccinations of the birds. In addition, we are not aware of immunomodulating features of HuSA in poultry. Infectious bursal disease and IB were chosen to establish possible interference of the PAMP challenge with obligatory vaccination via the respiratory route.
Lipoteichoic acid, and to a minor degree also LPS, administered i.t. enhanced the secondary total Ab response and the IgG isotype response to HuSA. Lipoteichoic acid also enhanced Ab titers to IBD and IB at various times after secondary challenge with HuSA. For LTA this was expected. Lipoteichoic acid, when administered i.v., consistently enhanced primary and secondary Ab responses (Maldonado et al., 2005). The effect of LTA on Ab titers to IBD and IB was less pronounced than with HuSA, but this might be related to the differences between PAMP treatments and sensitization schedules between (the dead or soluble antigen) HuSA and (the live or particulate) vaccines. Lipoteichoic acid was shown to stimulate IL-6 mRNA and IL-6 release by human endothelial cells (Talreja et al., 2004) and, as a consequence, may enhance the TH-2 route of an immune response. However, gram-positive bacteria, of which LTA is an important part of the cell wall, may also induce more IL-12 than IL-10 in human monocytes in vitro (Hessle et al., 2000), suggesting that gram-positive bacteria can also stimulate TH-1 (cellular) immune responses. For LPS the data showed the opposite of our findings from previous work (Maldonado et al., 2005). In the former study, LPS enhanced in vitro cellular immunity, suggesting activation of a TH-1-like route by LPS and polarization of immune responses to other antigens in this direction. Previously, intravenously administered LPS decreased Ab responses (Parmentier et al., 2004) in poultry. However, LPS was also reported to induce more IL-10 than IL-12 production in vitro, although less than did intact gram-negative bacteria (Hessle et al., 2000). Repeated exposure of mice to LPS may result in enhanced production of IL-10 as a regulatory response to the LPS-induced production of IL-12 (Varma et al., 2005). Repeated LPS injections may cause chickens to become refractory to the LPS stimulus (Korver et al., 1998). Functional tolerance to LPS may be an active process, including enhanced expression of IL-10, which down-regulates production of proinflammatory cytokines (Ziegler-Heitbrock, 1995). Taken together, these results suggest that LPS may not always polarize immune responses to the TH-1 route, but may even enhance TH-2-like responses after repeated or chronic exposure to LPS, as found in the present experiment. The setup of the present study did not allow us to measure cytokines during the course of the Ab response to HuSA. Our data suggest, however, that LPS can also differentially modulate the immune response via different pathways of cell activation. Thus, immune modulation by PAMP probably depends on the route of challenge, dose, and duration of challenge, either in the presence of antigen or not.
Pathogen-associated molecular patterns were administered twice for 5 consecutive days to mimic a semichronic effect, although the dose was 500 times higher per day than the amount normally inhaled daily by a healthy chicken kept under battery conditions. The applied dose was based on earlier studies in which i.v. or intraperitoneally administered LPS modulated immune responses and BW (gain). Earlier we determined levels of airborne LPS in our animal facilities that were comparable with levels reported in literature (data not shown). All birds treated i.t. with PAMP showed a reduced BW (gain) during the complete observation period, suggesting that indeed hygiene in a chicken house is related to the growth and production features of food animals. However, effects of PAMP exposure on BW gain, as a parameter of cachectin activity, were found especially on the first day of the 5 consecutive days of PAMP challenge, both during primary (LPS) and secondary (LPS and BGL) challenges. Either the cachectin response to LPS after 1 d was exhausted, or daily administration of LPS caused a refractive status of the birds toward LPS (Korver et al., 1998). Finally, we observed a classic T-cell-dependent-like Ab response to LPS (Figure 2), but not to the other PAMP, after both primary and secondary challenge. Intratracheally administered LPS may behave differently from i.v. administered LPS. Whether this is related to the well-developed bronchus-associated lymphoid tissue in birds (Reese et al., 2006) remains to be established. Alternatively, the short latent periods after both primary and secondary i.t. challenges with LPS suggest earlier sensitization with airborne LPS, which might have sensitized the birds for memory-like responses to LPS.
Intratracheal administration of LTA and LPS significantly affected secondary Ab responses, especially IgG and, to a minor extent, IgA responses. Pathogen-associated molecular patterns may affect dendritic cells, and consequently memory T-cell responses, or alternatively, may directly bind memory B cells, maintaining a nonantigen-specific form of memory (Bernasconi et al., 2003). Levels of natural Ab (binding keyhole limpet hemocyanin), classical and alternative complement activity, and in vitro proliferative responses to concanavalin A and HuSA were not affected (data not shown). In a simultaneous study, cytokine mRNA levels after primary i.t. LPS challenge induced no consistent changes in the levels of TH-1- or TH-2-related cytokines (data not shown). To establish molecular routes of the effect of airborne PAMP on Ab responses in chickens, future studies should thus address cytokine profiles in the early phase of the secondary Ab response, both in the respiratory tract and in lymphoid tissues such as the spleen, and should include various doses of PAMP and model antigens administered via the i.t. route.
Chronic exposure to airborne endotoxins was previously related to respiratory (hypersensitivity) diseases in farmers (Douwes, 1998; Douwes et al., 2004), and may also be a growing problem in current poultry husbandry. The respiratory inflammation frequently found in broilers was attributed to LPS, even after cessation of the experimental LPS challenge. Food animals kept under clean hygienic conditions grow faster and produce better. In the present study, we observed a high cumulative number of dead birds (58%) after i.t. LPS administration. Dissection of the birds revealed no pathology. Neither primary cannibalism nor feather pecking explained this observation. Humans with chronic heart failure have shown cellular hypersensitivity to LPS and a higher capacity for tumor necrosis factor-
generation (Krüger et al., 2004). Long-term i.t. exposure to LPS has been shown to induce production of proinflammatory cytokines, persistent pathology, and chronic lung inflammation in mice (Ishii et al., 1997; Vernooy et al., 2002) and increased pulmonary arterial pressure (Wideman et al., 2004; Chapman et al., 2005) in chickens, most of which are acute reactions. In our study, death of chickens occurred a few weeks after the i.t. LPS treatments, excluding an acute response to LPS. A relation with the vaccination scheme remained unclear, but 2 IB vaccinations and 1 infectious laryngotracheitis vaccination, both sprays, were administered within a period of 6 wk following the primary i.t. challenge with LPS.
We concluded that immune modulation by airborne PAMP is possible; i.t. administered LTA and, to a minor extent, also LPS enhanced secondary Ab responses of hens to HuSA and vaccine titers. Tracheal challenge may be a useful model to mimic the hygiene status of a chicken house, although additional studies on the penetration or localization of i.t. administered PAMP in the airways are required. Immune modulation by airborne PAMP may have consequences for the health status of an animal (Sainsbury, 1992; Appleby et al., 2004). Modulation of immune responses may add to a higher resistance to certain infections or efficacy of vaccines, but also result in unwanted hypersensitivity or allergy, or decreased resistance to other infections. The continuous presence of airborne PAMP on farms might be related to respiratory disorders and suboptimal health. This necessitates further knowledge of the effects of airborne PAMP on the immune system as well as of optimal zootechnical and health management procedures. A mechanistic basis underlying the proposed deleterious, but also possibly advantageous, effects of PAMP (LPS, LTA, BGL, cytosine phosphate guanine DNA, heat shock proteins, uric acid) on the health of animals is unknown. In addition, the effects of acute or chronic (either repeated or crossover) exposure of different doses of PAMP at different ages are unknown. Recently, we found that repeated i.t. exposure of young layers with PAMP affected Ab responses differently as compared with crossover responses with different PAMP (Parmentier et al., 2006). These subjects, and the relation between PAMP exposure and activation of the immune system of chickens, are currently under study.
Received for publication January 12, 2007. Accepted for publication April 15, 2007.
|
REFERENCES |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
Barnes, D. M., Z. Song, K. C. Klasing, and W. Bottje. 2002. Protein metabolism during an acute phase response in chickens. Amino Acids 22:15–26.[ISI][Medline]
Bernasconi, N., N. Onai, and A. Lanzaveccia. 2003. A role for Toll like receptors in acquired immunity: Upregulation of TLR9 by BCR triggering in naïve B cells and constitutive expression in memory B cells. Blood 101:4500–4504.
Calkins, C. M., K. Barsness, D. D. Bensard, A. Vasquez-Torres, C. D. Raeburn, X. Meng, and R. C. McIntyre, Jr. 2002. Toll-like receptor-4 signalling mediates pulmonary neutrophil sequestration in response to gram-positive bacterial entero-toxin. J. Surg. Res. 104:124–130.[ISI][Medline]
Chapman, M. E., W. Wang, G. F. Erf, and R. F. Wideman, Jr. 2005. Pulmonary hypertensive responses of broilers to bacterial lipopolysaccharide (LPS): Evaluation of LPS source and dose, and impact of pre-existing pulmonary hypertension and cellulose micro-particle selection. Poult. Sci. 84:432–441.
Douwes, J. 1998. Respiratory health effects of indoor microbial exposure. A contribution to the development of exposure assessment methods. PhD Thesis. Wageningen Univ., the Netherlands.
Douwes, J., G. Le Gros, and N. Pearce. 2004. Can bacterial endo-toxin exposure reverse atopy and atopic disease? J. Allergy Clin. Immunol. 5:1051–1054.
Dusseldorp, A., M. Van Bruggen, J. Douwes, P. J. C. M. Janssen, and G. Kelfkens. 2004. Gezondheidkundige advieswaarden binnenmilieu. RIVM Rapport 609021029/2004. Rijksinstituut Volksgezond. Milieu, Bilthoven, the Netherlands.
Frasnelli, M. E., D. Tarussio, V. Chobaz-Péclat, N. Busso, and A. So. 2005. TLR2 modulates inflammation in zymosan-induced arthritis in mice. Arthritis Res. Ther. 7:R370–R379.[ISI][Medline]
Hessle, C., B. Andersson, and A. E. Wold. 2000. Gram-positive bacteria are potent inducers of monocytic interleukin-12 (IL- 12) while gram-negative bacteria preferentially stimulate IL-10 production. Infect. Immun. 68:3581–3586.
Ishii, S., T. Nagase, F. Tashiro, K. Ikuta, S. Sato, I. Waga, K. Kume, J. Miyazaki, and T. Shimuzu. 1997. Bronchial hyperreactivity, increased endotoxin lethality and melanocytic tumorogenesis in transgenic mice overexpressing platelet-activating factor receptor. EMBO J. 16:133–142.[ISI][Medline]
Kao, S. J., H. C. Lei, C. T. Kuo, M. S. Chang, B. C. Chen, Y. C. Chang, W. T. Chiu, and C. H. Lin. 2005. Lipoteichoic acid induces nuclear factor-B activation and nitric oxide synthase expression via phosphatidylinositol 3-kinase, Akt, and p38 MAPK in RAW 264.7 macrophages. Immunology 115:366–374.[ISI][Medline]
Kapsenberg, M. L. 2003. Dendritic-cell control of pathogen-driven T-cell polarization. Nat. Rev. Immunol. 3:984–993.[ISI][Medline]
Korver, D. R., E. Roura, and K. C. Klasing. 1998. Effect of dietary energy level and oil source on broiler performance and response to an inflammatory challenge. Poult. Sci. 77:1217–1227.
Krüger, S., D. Kunz, J. Graf, T. Stickel, M. W. Merx, P. Hanrath, and U. Janssens. 2004. Endotoxin sensitivity and immune competence in chronic heart failure. Clin. Chim. Acta 343:135–139.[ISI][Medline]
Lee, C. W., C. S. Chien, and C. M. Yang. 2004. Lipoteichoic acid-stimulated p42/p44 MAPK activation via Toll-like receptor 2 in tracheal smooth muscle cells. Am. J. Physiol. Lung Cell. Mol. Physiol. 286:921–930.
Ma, Y. G., M. Y. Cho, M. Zhao, J. W. Park, M. Matsushita, T. Fujita, and B. L. Lee. 2004. Human mannose-binding lectin and L-ficolin function as specific pattern recognition proteins in the lectin activation pathway of complement. J. Biol. Chem. 279:25307–25312.
Maldonado, L. M. E., A. Lammers, M. G. B. Nieuwland, G. De Vries Reilingh, and H. K. Parmentier. 2005. Homotopes affect primary and secondary antibody responses in poultry. Vaccine 23:2731–2739.[ISI][Medline]
Parmentier, H. K., W. J. A. Van den Kieboom, M. G. B. Nieuwland, G. De Vries Reilingh, B. N. Hangalapura, H. F. J. Savelkoul, and A. Lammers. 2004. Differential effects of lipopolysaccharide and lipoteichoic acid on the primary antibody response to keyhole limpet hemocyanin of chickens selected for high or low antibody responses to sheep red blood cells. Poult. Sci. 83:1133–1139.
Parmentier, H. K., L. Star, S. C. Sodoyer, M. G. B. Nieuwland, G. De Vries Reilingh, A. Lammers, and B. Kemp. 2006. Age-and breed-dependent adapted immune responsiveness of poultry to intratracheal-administered, pathogen-associated molecular patterns. Poultry Sci. 85:2156–2168.
Pelizon, A. C., R. Kaneno, A. M. V. C. Soares, D. A. Meira, and A. Sartori. 2003. Down-modulation of lymphoproliferation and interferon-
production by ß-glucan derived from Saccharomyces cerevisiae. Mem. Inst. Oswaldo Cruz 98:1083–1087.[ISI][Medline]
Powers, W. J., C. R. Angel, and T. J. Applegate. 2005. Air emissions in poultry production: Current challenges and future directions. J. Appl. Poult. Res. 14:613–621.
Reese, S., G. Dalamani, and B. Kaspers. 2006. The avian lung-associated immune system: A review. Vet. Res. 37:311–324.[ISI][Medline]
Rocksen, D., B. Koch, T. Sandstrom, and A. Bucht. 2004. Lung effects during a generalized Shwartzman reaction and therapeutic intervention with dexamethasone or vitamin E. Shock 22:482–490.[ISI][Medline]
Sainsbury, D. 1992. Poultry Health and Management: Chickens, Ducks, Turkeys, Geese, Quail. Blackwell Sci. Publ., Oxford, UK.
SAS Institute. 1990. SAS User’s Guide: Statistics. Version 6 ed. SAS Inst. Inc., Cary, NC.
Sjöstrand, M., and R. Rylander. 1997. Pulmonary cell infiltration after chronic exposure to (1
3)-ß-glucan and cigarette smoke. Inflamm. Res. 46:93–97.[ISI][Medline]
Talreja, J., M. H. Kabir, M. B. Filla, D. J. Stechschulte, and K. N. Dileepan. 2004. Histamine induces Toll-like receptor 2 and 4 expression in endothelial cells and enhances sensitivity to Gram-positive and Gram-negative bacterial cell wall components. Immunology 113:224–233.[ISI][Medline]
Varma, T. K., M. Durham, E. D. Murphey, W. Cui, Z. Huang, C. Y. Z. Lin, T. Toliver-Kinsky, and E. R. Sherwood. 2005. Endotoxin priming improves clearance of Pseudomonas aeruginosa in wild-type and interleukin-10 knockout mice. Infect. Immun. 73:7340–7347.
Vernooy, J. H., M. A. Dentener, R. J. Van Suylen, W. A. Buurman, and E. F. M. Wouters. 2002. Long-term intratracheal lipopolysaccharide exposure in mice results in chronic lung inflammation and persistent pathology. Am. J. Respirat. Cell. Mol. Biol. 26:152–159.
Werling, D., and T. W. Jungi. 2002. Toll-like receptors linking innate and adaptive immune response. Vet. Immunol. Immunopathol. 91:1–12.[ISI]
Wideman, R. F., M. E. Chapman, W. Wang, and G. F. Erf. 2004. Immune modulation of the pulmonary hypertensive response to bacterial lipopolysaccharide (endotoxin) in broilers. Poult. Sci. 83:624–637.
Young, S. H., V. A. Robinson, M. Barger, D. W. Porter, D. G. Frazer, and V. Castranova. 2001. Acute inflammation and recovery in rats after intratracheal instillation of a 13-ß-glucan (Zymosan A). J. Toxicol. Environ. Health 64:311–325.[ISI]
Ziegler-Heitbrock, H. W. 1995. Molecular mechanism in tolerance to lipopolysaccharide. J. Inflamm. 45:13–26.[ISI][Medline]
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
), lipoteichoic acid (LTA; 
), Zymosan-A containing 1,3 ß-glucan (BGL; 
), or PBS (•), and similarly, 3 mo later after subcutaneous immunization with HuSA after intratracheal challenge for 5 consecutive days with LPS, LTA, BGL, or PBS. Data represent mean antibody titers at d –8, 3, 6, 13, 20, and 28 after primary immunization with HuSA, and d –15, 3, 7, 10, and 14 after secondary immunization with HuSA, as estimated by ELISA of serial dilutions of sera from 11 to 12 birds (primary immunization) or 9 to 12 birds (secondary immunization) per treatment group and using 1:20,000 diluted rabbit antichicken IgGH+L coupled to peroxidase (total Ig), 1:20,000 diluted goat antichicken IgM coupled to peroxidase (IgM), 1:20,000 diluted goat antichicken IgGFc coupled to peroxidase (IgG), or 1:20,000 diluted goat antichicken IgA coupled to peroxidase (IgA). a,bMeans with different letters per sample time points differ (P < 0.05).
