scholarly journals Cytokine Gene Expression in Peripheral Blood Mononuclear Cells and Tissues of Cattle Infected with Mycobacterium avium subsp. paratuberculosis: Evidence for an Inherent Proinflammatory Gene Expression Pattern

2004 ◽  
Vol 72 (3) ◽  
pp. 1409-1422 ◽  
Author(s):  
Paul M. Coussens ◽  
Nitin Verman ◽  
Marc A. Coussens ◽  
Michael D. Elftman ◽  
Amanda M. McNulty
Keyword(s):  
Gene Expression ◽  
Lymph Nodes ◽  
Mononuclear Cells ◽  
Gene Expression Pattern ◽  
Cytokine Gene Expression ◽  
Infected Cattle ◽  
Mesenteric Lymph Nodes ◽  
Mesenteric Lymph ◽  
Genes Encoding ◽  
Ifn Γ

ABSTRACT In cattle and other ruminants, infection with the intracellular pathogen Mycobacterium avium subsp. paratuberculosis results in a granulomatous enteritis (Johne's disease) that is often fatal. The key features of host immunity to M. avium subsp. paratuberculosis infection include an appropriate early proinflammatory and cytotoxic response (Th1-like) that eventually gives way to a predominant antibody-based response (Th2-like). Clinical disease symptoms often appear subsequent to waning of the Th1-like immune response. Understanding why this shift in the immune response occurs and the underlying molecular mechanisms involved is critical to future control measures and diagnosis. Previous studies have suggested that M. avium subsp. paratuberculosis may suppress gene expression in peripheral blood mononuclear cells (PBMCs) from infected cows, despite a continued inflammatory reaction at sites of infection. In the present study, we tested the hypothesis that exposure to M. avium subsp. paratuberculosis suppresses a proinflammatory gene expression pattern in PBMCs from infected cows. To do this, we examined expression of genes encoding interleukin-1α (IL-1α), IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p35, IL-16, and IL-18, as well as genes encoding gamma interferon (IFN-γ), transforming growth factor β (TGF-β), and tumor necrosis factor alpha (TNF-α), in PBMCs, intestinal lesions, and mesenteric lymph nodes of cattle naturally infected with M. avium subsp. paratuberculosis. Cytokine gene expression in these cells and tissues was compared to expression in similar cells and tissues from control uninfected cattle. Our comprehensive results demonstrate that for most cytokine genes, including the genes encoding IFN-γ, TGF-β, TNF-α, IL-1α, IL-4, IL-6, IL-8, and IL-12p35, differential expression in PBMCs from infected and control cattle did not require stimulation with M. avium subsp. paratuberculosis. In fact, stimulation with M. avium subsp. paratuberculosis tended to reduce the differential expression observed in infected and uninfected cows for genes encoding IFN-γ, IL-1α, and IL-6. Only IL-10 gene expression was consistently enhanced by M. avium subsp. paratuberculosis stimulation of PBMCs from subclinically infected cattle. In ileal tissues from M. avium subsp. paratuberculosis-infected cattle, expression of the genes encoding IFN-γ, TGF-β, IL-5, and IL-8 was greater than the expression in comparable tissues from control uninfected cattle, while expression of the gene encoding IL-16 was lower in tissues from infected cattle than in control tissues. Mesenteric lymph nodes draining sites of M. avium subsp. paratuberculosis infection expressed higher levels of IL-1α, IL-8, IL-2, and IL-10 mRNA than similar tissues from control uninfected cattle expressed. In contrast, the genes encoding TGF-β and IL-16 were expressed at lower levels in lymph nodes from infected cattle than in tissues from uninfected cattle. Taken together, our results suggest that cells or other mechanisms capable of limiting proinflammatory responses to M. avium subsp. paratuberculosis develop in infected cattle and that a likely place for development and expansion of these cell populations is the mesenteric lymph nodes draining sites of infection.

Establishment of tolerance to commensal bacteria requires a complex microbiota and is accompanied by decreased intestinal chemokine expression

2012 ◽  
Vol 302 (1) ◽  
pp. G55-G65 ◽  
Author(s):  
L. N. Fink ◽  
S. B. Metzdorff ◽  
L. H. Zeuthen ◽  
C. Nellemann ◽  
M. B. Kristensen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lymph Nodes ◽  
Ex Vivo ◽  
Gene Expression Pattern ◽  
Mesenteric Lymph Nodes ◽  
Microbial Detection ◽  
E Coli ◽  
Germ Free ◽  
Expression Of Genes ◽  
Genes Encoding

Intricate regulation of tolerance to the intestinal commensal microbiota acquired at birth is critical. We hypothesized that epithelial cell tolerance toward early gram-positive and gram-negative colonizing bacteria is established immediately after birth, as has previously been shown for endotoxin. Gene expression in the intestine of mouse pups born to dams that were either colonized with a conventional microbiota or monocolonized ( Lactobacillus acidophilus or Eschericia coli ) or germ free was examined on day 1 and day 6 after birth. Intestinal epithelial cells from all groups of pups were stimulated ex vivo with L. acidophilus and E. coli to assess tolerance establishment. Intestine from pups exposed to a conventional microbiota displayed lower expression of Ccl2, Ccl3, Cxcl1, Cxcl2, and Tslp than germ-free mice, whereas genes encoding proteins in Toll-like receptor signaling pathways and cytokines were upregulated. When comparing pups on day 1 and day 6 after birth, a specific change in gene expression pattern was evident in all groups of mice. Tolerance to ex vivo stimulation with E. coli was only established in conventional animals. Colonization of the intestine was reflected in the spleen displaying downregulation of Cxcl2 compared with germ-free animals on day 1 after birth. Colonization reduced the expression of genes involved in antigen presentation in the intestine-draining mesenteric lymph nodes, but not in the popliteal lymph nodes, as evidenced by gene expression on day 23 after birth. We propose that microbial detection systems in the intestine are upregulated by colonization with a diverse microbiota, whereas expression of proinflammatory chemokines is reduced to avoid excess recruitment of immune cells to the maturing intestine.

scholarly journals Expression of Regulatory T Cells in Jejunum, Colon, and Cervical and Mesenteric Lymph Nodes of Dogs Naturally Infected with Leishmania infantum

2014 ◽  
Vol 82 (9) ◽  
pp. 3704-3712 ◽  
Author(s):  
Maria M. Figueiredo ◽  
Beatriz Deoti ◽  
Izabela F. Amorim ◽  
Aldair J. W. Pinto ◽  
Andrea Moraes ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Lymph Nodes ◽  
Leishmania Infantum ◽  
Parasite Load ◽  
Mesenteric Lymph Nodes ◽  
Content Type ◽  
Mesenteric Lymph ◽  
Tnf Α ◽  
Ifn Γ

ABSTRACTUsing flow cytometry, we evaluated the frequencies of CD4+and CD8+T cells and Foxp3+regulatory T cells (Tregs) in mononuclear cells in the jejunum, colon, and cervical and mesenteric lymph nodes of dogs naturally infected withLeishmania infantumand in uninfected controls. All infected dogs showed chronic lymphadenitis and enteritis. Despite persistent parasite loads, no erosion or ulcers were evident in the epithelial mucosa. The colon harbored more parasites than the jejunum. Frequencies of total CD4+, total Foxp3, and CD4+Foxp3+cells were higher in the jejunum than in the colon. Despite negative enzyme-linked immunosorbent assay (ELISA) serum results for cytokines, levels of interleukin-10 (IL-10), gamma interferon (IFN-γ), transforming growth factor beta (TGF-β), and tumor necrosis factor alpha (TNF-α) were higher in the jejunum than in the colon for infected dogs. However, IL-4 levels were higher in the colon than in the jejunum for infected dogs. There was no observed correlation between clinical signs and histopathological changes or immunological and parasitological findings in the gastrointestinal tract (GIT) of canines with visceral leishmaniasis. However, distinct segments of the GIT presented different immunological and parasitological responses. The jejunum showed a lower parasite load, with increased frequencies and expression of CD4, Foxp3, and CD8 receptors and IL-10, TGF-β, IFN-γ, and TNF-α cytokines. The colon showed a higher parasite load, with increasing expression of IL-4.Leishmania infantuminfection increased expression of CD4, Foxp3, IL-10, TGF-β, IFN-γ, and TNF-α and reduced CD8 and IL-4 expression in both the jejunum and the colon.

scholarly journals High prevalence of extrapulmonary tuberculosis in dairy farms: Evidence for possible gastrointestinal transmission

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0249341
Author(s):  
Fang Xu ◽  
Lili Tian ◽  
Yan Li ◽  
Xuelian Zhang ◽  
Yayin Qi ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Extrapulmonary Tuberculosis ◽  
Dairy Farms ◽  
Close Relation ◽  
Mesenteric Lymph Nodes ◽  
Mesenteric Lymph ◽  
Transmission Modes ◽  
High Prevalence ◽  
Ifn Γ ◽  
Wild Life

Bovine tuberculosis (bTB) caused by Mycobacterium bovis (M. bovis) represents one of major zoonotic diseases among cattle, it also affects the health of human, other domestic animals and wild life populations. Inhalation of infected aerosol droplets is considered as the most frequent route of the infection. This study aims to investigate the current forms of tuberculosis in cattle and identify the possible transmission modes in dairy farms of China. 13,345 cows from eight dairy farms in three provinces were comprehensively diagnosed by a multitude of assays, including SIT, CIT, IFN-γ assay and ELISA. It has been indicated that advanced infection of bTB was found in 752 (5.64%) cattle, suggesting a high prevalence of tuberculosis in these dairy farms. In the necropsy examination of 151 positive cattle, typical bTB lesions were observed in 131 cattle (86.75%), of which, notably, 90.84% lesions appeared in liver, spleen, mesenteric lymph nodes, mammary lymph nodes and other organs, taking up a large proportion among cattle with advanced bTB infection. 71.26% extrapulmonary tuberculosis (EPTB) was related to gastrointestinal system. M. bovis nucleic acid was further found in milk and feces samples and M. bovis was even isolated from milk samples. Phylogenetic analysis based on whole genome sequencing unraveled that six isolates were closely related to M. bovis AF2122/97 originated from UK, whereas four isolates shared close relation to M. bovis 30 from China, respectively. Our data demonstrate that the increase of EPTB transmitted by digestive tract is implicated in the current high prevalence rate of bTB in China, which also provides leads for bTB control in other countries with high prevalence of bTB in the future.

Rotavirus A associated pathology of intestine and mesenteric lymph nodes and occurrence in bovine calves of Gwalior and Bareilly regions

2018 ◽  
Author(s):  
Gayatri Kashyap ◽  
R. Singh ◽  
Y. S. Malik ◽  
R. K. Agrawal ◽  
K. P. Singh ◽  
...  
Keyword(s):  
Small Intestine ◽  
Lymph Nodes ◽  
Mononuclear Cells ◽  
Dairy Farm ◽  
Rt Pcr ◽  
Mesenteric Lymph Nodes ◽  
Fecal Samples ◽  
Rotavirus A ◽  
Mesenteric Lymph ◽  
Vp6 Gene

To understand the pathology of natural cases of rotavirus (RVA) in bovine calves, a total of 40 cases below 6 months died due to diarrhoea were studied, out of which 7 cases (17.5%) turned positive for RVA by RT-PCR. Histopathology of small intestine showed loss of villous enterocytes, blunting and fusion of villi, elongation of crypts and mononuclear cells infiltration in the lamina-propria. The mesenteric lymph nodes were severely depleted of lymphocytes. These changes were corroborated with presence of RVA antigen in sections by dFAT and nucleic acid by RT-PCR. The fluorescent signals were more in mesenteric lymph nodes than in intestine. Besides, 115 rectal fecal samples were also collected from calves for RVA detection by RT-PCR using VP6 gene specific sets of primers. Dead carcasses of calves (n= 40) belonged to organized dairy farm of Bareilly, while rectal fecal samples belonged to both organized (n= 38) and unorganized farms (n= 77) of Bareilly and Gwalior. The overall occurrence of RVA was 19.3% (30/155), comprising 5/37 cases (13.5%) from Gwalior (MP) and 25/118 cases (21.1%) from Bareilly (UP). These findings suggest the infection of RVA widely prevalent in calves and have potential to escape from the intestinal site to mesenteric lymph nodes.

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