transforming-growth-factor-beta and Salmonella-Infections--Animal

Salmonellosis in poultry is a serious economic burden. A major concern is the public health hazard caused by consumption of. A. We demonstrated targeting of surface F-protein coated chitosan NPs to immune cells when delivered orally to layer chickens, the particles were localized in ileal Peyer's patches. The OMPs-F-CS NPs vaccinated layer chickens had significantly higher OMPs-specific mucosal IgA production and lymphocyte proliferation response. The candidate vaccine increased the expression of toll-like receptor (TLR)-2, TLR-4, IFN-γ, TGF-ß and IL-4 mRNA expression in chicken cecal tonsils.. Our study demonstrated that the chitosan-based oral

Topics: Administration, Oral; Animals; Chickens; Chitosan; Female; Immunity, Cellular; Interleukin-4; Intestinal Mucosa; Nanoparticles; Porins; Salmonella enteritidis; Salmonella Infections, Animal; Salmonella Vaccines; Toll-Like Receptors; Transforming Growth Factor beta; Vaccines, Subunit

The relative mRNA expression of IgA, TGF-β4, IL-17, and concentration of secretory IgA (sIgA) in small intestine of chickens pretreated with Enterococcus faecium AL41 and challenged with Salmonella Enteritidis PT4 were studied. Salmonella-free day-old chicks (40) Cobb 500 breed, were divided into four groups of 10 chicks each (n = 10): control (C), treated with E. faecium AL41 strain (EFAL41), challenged with Salmonella Enteritidis PT4 (SE), and combined (EFAL41+SE). Expression of IgA and sIgA concentration was upregulated in EFAL41 group in jejunum and ileum on 4 days post-Salmonella infection (dpi). Chicks in combined group demonstrated upregulation of cytokines and IgA expression, and increased sIgA concentration in the intestine flush on 7 dpi. The experiment demonstrated beneficial effect of E. faecium AL41 on IgA production and secretion in intestine. Findings also indicated that IgA played important role in decrease of S. Enteritidis in the intestine, and cytokines TGF-β4 and IL-17 contributed to the increased IgA secretion.

Topics: Animal Feed; Animals; Avian Proteins; Chickens; Cytokines; Diet; Enterococcus faecium; Enzyme-Linked Immunosorbent Assay; Immunoglobulin A; Interleukin-17; Intestine, Small; Poultry Diseases; Probiotics; Random Allocation; Real-Time Polymerase Chain Reaction; RNA, Messenger; Salmonella enteritidis; Salmonella Infections, Animal; Transforming Growth Factor beta; Up-Regulation

Infection of chicken with Salmonella may lead to a carrier-state characterized by the persistence of bacteria in the ceca for a long period of time and result in their excretion in feces. This excretion is the source of contamination of their congeners and food. During infection, enterocytes are the primary target cells for Salmonella, the producers of soluble factors which launch immune response and cells which are reciprocally responsive to surrounding immune cells. This study used microarrays to compare the gene expression profile during carrier-state of enterocytes purified from infected and control chicks which are either resistant or susceptible to Salmonella Enteritidis carrier-state. In total, we identified 271 genes significantly differentially expressed with an absolute fold change greater than 1.5. A global analysis determined interaction networks between differentially regulated genes. Using an a priori approach, our analyses focused on differentially expressed genes which were transcriptionally linked to cytokines playing a major role in the fate of the immune response. The expression of genes transcriptionally linked to type I interferon and TGF-β was down-regulated in infected chicks from both lines. Gene expression linked to the Th1 axis suggests the latter is inhibited in both lines. Finally, the expression of genes linked to IL-4, IL-5 and IL-13 indicates that susceptibility to carrier-state could be associated with a Th2 bias. Overall, these results highlight that the response to Salmonella during the acute phase and carrier-state is different and that enterocytes play a central role in this response.

Topics: Animals; Carrier State; Chickens; Disease Susceptibility; Enterocytes; Gene Expression Profiling; Gene Expression Regulation, Bacterial; Interferon Type I; Oligonucleotide Array Sequence Analysis; Poultry Diseases; Real-Time Polymerase Chain Reaction; Salmonella enteritidis; Salmonella Infections, Animal; Specific Pathogen-Free Organisms; Transforming Growth Factor beta

Developing efficacious vaccines against enteric diseases is a global challenge that requires a better understanding of cellular recruitment dynamics at the mucosal surfaces. The current paradigm of T cell homing to the gastrointestinal (GI) tract involves the induction of α4β7 and CCR9 by Peyer's patch and mesenteric lymph node (MLN) dendritic cells (DCs) in a retinoic acid-dependent manner. This paradigm, however, cannot be reconciled with reports of GI T cell responses after intranasal (i.n.) delivery of antigens that do not directly target the GI lymphoid tissue. To explore alternative pathways of cellular migration, we have investigated the ability of DCs from mucosal and nonmucosal tissues to recruit lymphocytes to the GI tract. Unexpectedly, we found that lung DCs, like CD103(+) MLN DCs, up-regulate the gut-homing integrin α4β7 in vitro and in vivo, and induce T cell migration to the GI tract in vivo. Consistent with a role for this pathway in generating mucosal immune responses, lung DC targeting by i.n. immunization induced protective immunity against enteric challenge with a highly pathogenic strain of Salmonella. The present report demonstrates novel functional evidence of mucosal cross talk mediated by DCs, which has the potential to inform the design of novel vaccines against mucosal pathogens.

Topics: Administration, Intranasal; Adoptive Transfer; Animals; Antigens, CD; Antigens, Surface; Basic-Leucine Zipper Transcription Factors; Cell Movement; Dendritic Cells; Fingolimod Hydrochloride; Gastrointestinal Tract; Immunity, Mucosal; Immunization; Integrins; Intestinal Mucosa; Lectins, C-Type; Lung; Mannose-Binding Lectins; Mice; Mice, Inbred C57BL; Propylene Glycols; Receptors, CCR; Salmonella; Salmonella Infections, Animal; Signal Transduction; Sphingosine; T-Lymphocytes; Transforming Growth Factor beta; Tretinoin

Resistance to pathogens such as Salmonella enteritidis (SE) is a heritable trait important in maintaining the health of chickens and reducing bacterial contamination of poultry products. In chickens, heterophils act as the first responders to bacterial infections and are, therefore, responsible for initiating the immune response against SE challenge. This study measured mRNA expression of several immune response genes [interleukin-6 (IL-6), IL-10, transforming growth factor-beta4 (TGF-beta4), granulocyte macrophage-colony stimulating factor (GM-CSF), and Toll-like receptor-4 (TLR-4)] by heterophils from broiler, Leghorn, and Fayoumi chickens, either non-stimulated or stimulated in vitro with SE using quantitative reverse-transcriptase PCR. We found that heterophils of commercially selected broiler and Leghorn birds had differing early heterophil responses to SE in comparison with the native Fayoumi line. Heterophil stimulation with SE in vitro increased expression of pro- (IL-6 and GM-CSF) and anti-inflammatory cytokine mRNA (IL-10 and TGF-beta4) in the Fayoumi line, while the broiler and Leghorn line heterophils had decreased or no changes in the cytokine gene expression levels. The unique response of the Fayoumi line is in contrast to the lines with a history of genetic selection to increase growth or reproduction, a process which may favor reduced or suppressed inflammatory responses. The findings illustrate the potential value of native lines to provide biodiversity to enhance innate health in commercially selected poultry.

Topics: Animals; Chickens; Cytokines; Gene Expression; Granulocyte-Macrophage Colony-Stimulating Factor; Granulocytes; In Vitro Techniques; Interleukin-10; Interleukin-6; Poultry Diseases; Quantitative Trait, Heritable; RNA, Messenger; Salmonella enteritidis; Salmonella Infections, Animal; Species Specificity; Toll-Like Receptor 4; Transforming Growth Factor beta

We recently showed that increased in vitro heterophil functional efficiency translates to increased in vivo resistance to a systemic Salmonella enteritidis (SE) infection utilizing a parental pair of broiler chickens (lines A and B) and the F1 reciprocal crosses (C and D). Heterophils produce cytokines and modulate acute protection against Salmonella in young poultry. Therefore, we hypothesize that heterophils from SE-resistant chickens (A and D) have the ability to produce an up-regulated pro-inflammatory cytokine response compared to that of heterophils from SE-susceptible chickens (B and C). In this study, heterophils were isolated from day-old chickens and treated with either RPMI-1640 (as the control), or phagocytic agonists (SE, or SE opsonized with either normal chicken serum or immune serum against SE) and cytokine mRNA expression assessed using real-time quantitative reverse transcription-polymerase chain reaction. Heterophils from SE-resistant chickens (A and D) had significantly higher levels of pro-inflammatory cytokine (interleukin (IL)-6, IL-8, and IL-18) mRNA expression upon treatment with all agonists compared to heterophils from SE-susceptible lines (B and C). Further, heterophils from SE-resistant chickens had significantly decreased mRNA expression levels of transforming growth factor-beta4, an anti-inflammatory cytokine, when compared to heterophils from SE-susceptible chickens. These data indicate cytokine gene expression in heterophils may be a useful parameter in determining resistance to Salmonella, as indicated by our previous in vivo SE studies. Therefore, heterophil functional efficiency and cytokine production may be useful biomarkers for poultry breeders to consider when developing new immunocompetent lines of birds.

Topics: Animals; Chickens; Cytokines; Disease Susceptibility; Gene Expression; Immunocompetence; Interleukin-18; Interleukin-6; Interleukin-8; Neutrophils; Poultry Diseases; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Salmonella Infections, Animal; Transforming Growth Factor beta

We have investigated the effect of the in vivo administration of recombinant transforming growth factor beta (rTGF-beta) on the pathogenic mechanisms involved in Salmonella typhimurium experimental infection in mice. The protective response elicited by macrophages was induced by rTGF-beta1 by 2 days after experimental infection, as demonstrated by an increased NO production, while the humoral protective effect began with cytokine mRNA expression 2 days after the challenge and continued after 5 days with cytokine release and lymphocyte activation. We demonstrated that all mice who received rTGF-beta1 survived 7 days after infection. The number of bacteria recovered in the spleens and in the livers of rTGF-beta1-treated mice 2 and 5 days after infection was significantly smaller than that found in the same organs after phosphate-buffered saline (PBS) inoculation. Furthermore, 2 and 5 days after infection, splenic macrophages from rTGF-beta1-treated mice showed a greater NO production than did those from PBS-treated mice. The effect of rTGF-beta1 on S. typhimurium infection in mice was correlated with the expression of cell costimulatory CD28 molecules. Five days after S. typhimurium infection, the percentage of CD28(+)-expressing T cells in splenic lymphocytes from rTGF-beta1-treated mice increased with respect to that from control mice. Gamma interferon (IFN-gamma) mRNA was present in a greater amount in spleen cells from rTGF-beta1-treated mice after 2 days, although the intensity of the band decreased 5 days after the challenge. A similar pattern was obtained with the mRNAs for interleukin-1alpha (IL-1alpha), IL-6, TGF-beta, and inducible nitric oxide synthase, which showed greater expression in cells obtained from rTGF-beta1-treated and S. typhimurium-infected mice 2 days after challenge. The treatment with rTGF-beta1 induced an increase in IL-1alpha and IFN-gamma release in the supernatant of splenocyte cultures 5 days after the experimental infection with S. typhimurium. Moreover, we demonstrated that 5 days after infection, the IFN-gamma titer was significantly greater in the sera of rTGF-beta-treated mice than in those of PBS-treated mice. Also, hsp60 showed greater expression 2 days after the challenge in splenocytes from rTGF-beta1-treated mice. The role played by proinflammatory and immunoregulatory cytokines and by CD28 is discussed.

Topics: Animals; CD28 Antigens; Chaperonin 60; Cytokines; Macrophages; Mice; Mice, Inbred BALB C; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Recombinant Proteins; RNA, Messenger; Salmonella Infections, Animal; Salmonella typhimurium; Transforming Growth Factor beta