Nunes, J.S. et al. Morphologic and cytokine profile characterization of Salmonella enterica serovar typhimurium infection in calves with bovine leukocyte adhesion deficiency. Vet. Pathol. 47, 322-333

Department of Veterinary Pathobiology, College of Veterinary Medicine, Texas A&M University, College Station, Texas, USA.
Veterinary Pathology (Impact Factor: 2.04). 03/2010; 47(2):322-33. DOI: 10.1177/0300985809358037
Source: PubMed

ABSTRACT The role of neutrophils in the pathogenesis of Salmonella enterica Typhimurium-induced ruminant and human enteritis and diarrhea has yet to be characterized with in vivo models. To address this question, the in vivo bovine ligated ileal loop model of nontyphoidal salmonellosis was used in calves with the naturally occurring bovine leukocyte adhesion deficiency (BLAD) mutation whose neutrophils are unable to extravasate and infiltrate the extravascular matrix. Data obtained from 4 BLAD Holstein calves homozygous for BLAD (CD18-), 1 to 5 weeks of age, were compared with 4 controls, age-matched Holstein calves negative for BLAD (CD18+). Morphologic studies revealed that infection of CD18- calves with S Typhimurium resulted in no significant tissue infiltration by neutrophils, less tissue damage, reduced luminal fluid accumulation, and increased bacterial invasion, when compared with CD18+ calves. Ultrastructurally, lesions in enterocytes induced by S Typhimurium infection in CD18- calves--including attachment and disruption of the brush border, apical membrane ruffling formation, and cellular degeneration--were similar to the ones reported in the literature for CD18- calves. Study of cytokine gene expression by quantitative real-time polymerase chain reaction revealed that early stages of acute infection (4-8 hours postinfection) were associated with increased interleukin 8 gene expression in the absence of tissue influx of neutrophils in CD18- calves, whereas later stages of infection (12 hours postinfection) were associated with increased expression of growth-related oncogene alpha in the presence of neutrophil influx in CD18+ calves. In contrast, the proinflammatory cytokines interleukin 1beta and tumor necrosis factor alpha were poorly correlated with the presence or absence of tissue neutrophils.

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    • "As a component of the innate host immune response, the inflammatory process should be seen as a host mechanism for preventing the spread of infection, which to some extent is completely correct, since in the absence of a neutrophilic response, Salmonella tends to spread more efficiently to systemic sites of infection, both in the mouse (53) as well as in cattle (54). These experimental observations parallel clinical disease since serotype Typhi that causes systemic infections does not elicit a significant intestinal neutrophilic response (10). "
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    ABSTRACT: Salmonella is a relevant pathogen under a clinical and public health perspective. Therefore, there has been a significant scientific effort to learn about pathogenic determinants of this pathogen. The clinical relevance of the disease, associated with the molecular tools available to study Salmonella as well as suitable animal models for salmonellosis, have provided optimal conditions to drive the scientific community to generate a large expansion of our knowledge about the pathogenesis of Salmonella-induced enterocolitis that took place during the past two decades. This research effort has also generated a wealth of information on the host immune mechanisms that complements gaps in the fundamental research in this area. This review focus on how the interaction between Salmonella, the microbiota and intestinal innate immunity leads to disease manifestation. As a highly successful enteropathogen, Salmonella actively elicits a robust acute intestinal inflammatory response from the host, which could theoretically lead to the pathogen demise. However, Salmonella has evolved redundant molecular machineries that renders this pathogen highly adapted to the inflamed intestinal environment, in which Salmonella is capable of outcompete resident commensal organisms. The adaptation of Salmonella to the inflamed intestinal lumen associated with the massive inflammatory response that leads to diarrhea, generate perfect conditions for transmission of the pathogen. These conditions illustrate the complexity of the co-evolution and ecology of the pathogen, commensals, and the host.
    Frontiers in Immunology 05/2014; 5:252. DOI:10.3389/fimmu.2014.00252
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    • "). S. Typhimurium infection of CD18- deficient calves, whose neutrophils are unable to extravasate, does not result in this severe epithelial damage (Nunes et al., 2010). This finding suggests that neutrophils are largely responsible for the collateral tissue damage accompanying exudative inflammation, thereby contributing to intestinal fluid accumulation and diarrhea. "
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    ABSTRACT: The intestinal immune system has to strike a delicate balance between initiating inflammatory responses against invading bacterial pathogens and avoiding their induction against microbiota colonizing the lumen. Adequate inflammatory responses against bacterial invasion result in the lumenal secretion of antimicrobial peptides, as well as the release of cytokines in tissue that recruit and activate phagocytes. However, pathogens have evolved to utilize these environmental changes in the inflamed intestine to promote colonization. This review focuses on the costs and benefits of intestinal inflammation and the fine interplay between the host, its microbiota, and enteric pathogens.
    Cell host & microbe 07/2010; 8(1):36-43. DOI:10.1016/j.chom.2010.06.003 · 12.19 Impact Factor
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    • "Similar results have been reported in Egypt (Moussa et al., 2010) and other countries of the world (Davies et al., 2004; Threlfal et al., 2006; Nunes et al., 2010). "
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