Mycobacterium avium subspecies induce differential expression of pro-inflammatory mediators in a murine macrophage model: Evidence for enhanced pathogenicity of Mycobacterium avium subspecies paratuberculosis

Basler, Tina; Geffers, Robert; Weiß, Siegfried; Valentin‐Weigand, Peter; Goethe, Ralph

doi:10.1016/j.imbio.2008.07.009

Cited by 20 publications

(21 citation statements)

References 36 publications

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“…M. paratuberculosis has been reported to induce early and persistent IL-10 expression that correlates with suppression of apoptosis (45). As macrophages exhibit different immunological responses following infection with different mycobacterial strains (3,47), we investigated whether this increase in IL-10 could be used to distinguish M. paratuberculosis strains of different virulence levels. There were no significant differences in IL-10 gene expression levels of macrophages infected with the different M. paratuberculosis strains, and although there were minor differences detected in the production of IL-10, it did not generally correlate with the attenuation of M. paratuberculosis strains in the models.…”

Section: Discussionmentioning

confidence: 99%

Assessment of Live Candidate Vaccines for Paratuberculosis in Animal Models and Macrophages

et al. 2010

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Mycobacterium avium subsp. paratuberculosis (basonym M. paratuberculosis) is the causative agent of paratuberculosis, a chronic enteritis of ruminants. To control the considerable economic effect that paratuberculosis has on the livestock industry, a vaccine that induces protection with minimal side effects is required. We employed transposon mutagenesis and allelic exchange to develop three potential vaccine candidates, which were then tested for virulence with macrophages, mice, and goats. All three models identified the WAg906 mutant as being the most attenuated, but some differences in the levels of attenuation were evident among the models when testing the other strains. In a preliminary mouse vaccine experiment, limited protection was induced by WAg915, as evidenced by a reduced bacterial load in spleens and livers 12 weeks following intraperitoneal challenge with M. paratuberculosis K10. While we found macrophages and murine models to be rapid and cost-effective alternatives for the initial screening of M. paratuberculosis mutants for attenuation, it appears necessary to do the definitive assessment of attenuation with a ruminant model.

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Section: Discussionmentioning

confidence: 99%

Assessment of Live Candidate Vaccines for Paratuberculosis in Animal Models and Macrophages

et al. 2010

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“…In vitro studies with macrophages have shown that in comparison to infection with M. avium subspecies avium (MAA) and M. avium subspecies hominissuis (MAH), MAP induces significantly less proinflammatory cytokines, including IL-1a, IL-1b, chemokine CXCL2, and TNF-a. 46 These findings might indicate that MAP is either not as immunogenic as MAA or MAH, or encodes for immunosuppressive effector protein. Regardless, increased TNF-a levels in culture supernatants from intestinal organ cultures from patients with CD correlated positively with the presence of MAP detected by nested polymerase chain reaction (PCR).…”

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confidence: 99%

Bacterial induction of proinflammatory cytokines in inflammatory bowel disease

Klapproth

Sasaki

2010

Inflammatory Bowel Diseases

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It has become increasingly clear that inflammatory bowel disease (IBD) develops on the background of genetic defects in the host, conveying an increased susceptibility to an environmental antigen or antigens. The environmental factor implicated in the pathophysiology of gut inflammation, which is undergoing increased scrutiny, is the intestinal flora. The intestinal flora as a whole and specific bacteria and their products have been found to trigger cytokine expression in various cell types. Consistently, multiple bacterial strains were found to induce tumor necrosis factor alpha (TNF-α) and interleukin-8 (IL-8) in macrophage and epithelial cell systems, respectively, in particular in Crohn's disease. Interestingly, various cell types from patients with IBD display an increased susceptibility to specific bacterial products, including flagellin, pili, and lipopolysaccharides. It remains to be determined whether additional effector proteins regulate cytokine expression and the aberrant mucosal immune response in IBD.

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“…In addition, similarly to NGAL, Q83 and the chicken homologue Ch21 seem to be involved in inflammation (11,12,55,56), tissue differentiation (13,28), and cancer progression (17,27). These similarities strongly suggest that Q83 and NGAL can be considered to represent siderocalin family members with comparable biological functionalities and emphasize the presumed pleitotropic functions of siderocalins.…”

Section: Discussionmentioning

confidence: 94%

“…Indeed, it has been shown that 24p3-deficient mice are more sensitive to bacterial infections (6 -8). Furthermore, Scn has been shown to be up-regulated upon inflammation (9,10) and to possibly exert proinflammatory effects (11,12).…”

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confidence: 99%

The v-myc-induced Q83 Lipocalin Is a Siderocalin

Coudevylle

Geist

Hötzinger

et al. 2010

Journal of Biological Chemistry

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Siderocalins are atypical lipocalins able to capture siderophores with high affinity. They contribute to the innate immune response by interfering with bacterial siderophore-mediated iron uptake but are also involved in numerous physiological processes such as inflammation, iron delivery, tissue differentiation, and cancer progression. The Q83 lipocalin was originally identified based on its overexpression in quail embryo fibroblasts transformed by the v-myc oncogene. We show here that Q83 is a siderocalin, binding the siderophore enterobactin with an affinity and mode of binding nearly identical to that of neutrophil gelatinase-associated lipocalin (NGAL), the prototypical siderocalin. This strengthens the role of siderocalins in cancer progression and inflammation. In addition, we also present the solution structure of Q83 in complex with intact enterobactin and a detailed analysis of the Q83 binding mode, including mutagenesis of the critical residues involved in enterobactin binding. These data provide a first insight into the molecular details of siderophore binding and delineate the common molecular properties defining the siderocalin protein family.

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Mycobacterium avium subspecies induce differential expression of pro-inflammatory mediators in a murine macrophage model: Evidence for enhanced pathogenicity of Mycobacterium avium subspecies paratuberculosis

Cited by 20 publications

References 36 publications

Assessment of Live Candidate Vaccines for Paratuberculosis in Animal Models and Macrophages

Assessment of Live Candidate Vaccines for Paratuberculosis in Animal Models and Macrophages

Bacterial induction of proinflammatory cytokines in inflammatory bowel disease

The v-myc-induced Q83 Lipocalin Is a Siderocalin

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