Premium
Immunoevasion and immunosuppression of the macrophage by M ycobacterium tuberculosis
Author(s) -
Hmama Zakaria,
PeñaDíaz Sandra,
Joseph Sunil,
AvGay Yossef
Publication year - 2015
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1111/imr.12268
Subject(s) - macrophage , biology , antigen presentation , phagosome , immune system , innate immune system , acquired immune system , major histocompatibility complex , immunology , mycobacterium tuberculosis , intracellular parasite , tuberculosis , microbiology and biotechnology , phagocytosis , t cell , medicine , genetics , pathology , in vitro
Summary By virtue of their position at the crossroads between the innate and adaptive immune response, macrophages play an essential role in the control of bacterial infections. Paradoxically, macrophages serve as the natural habitat to Mycobacterium tuberculosis (Mtb). Mtb subverts the macrophage's mechanisms of intracellular killing and antigen presentation, leading ultimately to the development of tuberculosis ( TB ) disease. Here, we describe mechanisms of Mtb uptake by the macrophage and address key macrophage functions that are targeted by Mtb‐specific effector molecules enabling this pathogen to circumvent host immune response. The macrophage functions described in this review include fusion between phagosomes and lysosomes, production of reactive oxygen and nitrogen species, antigen presentation and major histocompatibility complex class II expression and trafficking, as well as autophagy and apoptosis. All these are Mtb‐targeted key cellular pathways, normally working in concert in the macrophage to recognize, respond, and activate ‘proper’ immune responses. We further analyze and discuss major molecular interactions between Mtb virulence factors and key macrophage proteins and provide implications for vaccine and drug development.