Review Paper: Modulation of Mononuclear Phagocyte Function byMycobacterium aviumsubsp.paratuberculosis

Abstract

Abstract. Pathogenic mycobacteria are highly adapted for survival within host mononuclear phagocytes. This is largely due to the organism's capacity to prevent macrophage activation, block phagosome acidification and maturation, and attenuate presentation of antigens to the immune system. Mycobacterium avium subsp. paratuberculosis (MAP) is one such organism that modulates the ruminant innate immune response. It is the causative agent in paratuberculosis, a chronic progressive granulomatous enteritis in ruminants. MAP initially interacts with cell membrane receptors on bovine mononuclear phagocytes and initiates cell signaling responses and phagocytosis. Mannosylated liparabinomannan (Man-LAM) is a major component of the MAP cell wall that interacts with the cell membrane of mononuclear phagocytes and may be a major virulence factor. Toll-like receptor 2 (TLR2) has been incriminated as major signaling receptor that binds to MAP and initiates signaling though the mitogen-activated protein kinase (MAPK)-p38 pathway. This pathway induces transcription of interleukin (IL)-10. Early production of IL-10 suppresses proinflammatory cytokines, chemokines, IL-12, and major histocompatability factor class-II expression. Both IL-10 dependent and IL-10 independent mechanisms appear to be involved in attenuation of phagosome acidification and phagolysosome fusion. Many of the suppressive effects of MAP on bovine mononuclear phagocytes can be reproduced by exposure of bovine monocytes to Man-LAM. Therefore, MAP Man-LAM-induced TLR2-MAPK-p38 signaling with resultant excessive IL-10 expression has emerged as one of the mechanisms by which MAP organisms suppress inflammatory, immune, and antimicrobial responses and promote their survival within host mononuclear phagocytes.

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

“…Several of the techniques that pathogenic mycobacteria use to limit apoptosis have been associated with the overexpression of 49). This anti-inflammatory cytokine suppresses TH1-type responses, necessary for the control of mycobacterial infections.…”

Can early host responses to mycobacterial infection predict eventual disease outcomes?

“…Antigen presenting cells such as the macrophages and dendritic cells are able to indicate the presence of infection by presenting pathogen-derived antigens on their cell surface. These cells also release a variety of signals in the form of cytokines and chemokines (Weiss and Souza, 2008). The initial response predominantly involves the antigen-specific release of interferon gamma (IFNγ) by T lymphocytes and as disease progresses this response is replaced by an antibody response.…”

“…While the IFNγ response is important in the cell-mediated control of intracellular pathogens like MAP it is not always a predictor of disease outcome (Jungersen et al, 2012). To counteract the host's immune response, MAP can also actively induce certain cytokines to suppress and evade immune cells; interleukin (IL)-10 and tumour growth factor (TGF)β are two such cytokines (Weiss and Souza, 2008). IL-10 can also reduce the ability of macrophages to kill intracellular MAP (Weiss et al, 2005).…”

Bovine paratuberculosis: recent advances in vaccine development

“…MAP is able to interfere with antigen presentation, hence subsequent adaptive responses (Weiss and Souza 2008). Our understanding of the adaptive immune response against mycobacteria in general, and against MAP more specifically, is far from complete.…”