Insights into battles between Mycobacterium tuberculosis and macrophages

Abstract

As the first line of immune defense for Mycobacterium tuberculosis (Mtb), macrophages also provide a major habitat for Mtb to reside in the host for years. The battles between Mtb and macrophages have been constant since ancient times. Triggered upon Mtb infection, multiple cellular pathways in macrophages are activated to initiate a tailored immune response toward the invading pathogen and regulate the cellular fates of the host as well. Toll-like receptors (TLRs) expressed on macrophages can recognize pathogen-associated-molecular patterns (PAMPs) on Mtb and mediate the production of immune-regulatory cytokines such as tumor necrosis factor (TNF) and type I Interferons (IFNs). In addition, Vitamin D receptor (VDR) and Vitamin D-1-hydroxylase are up-regulated in Mtb-infected macrophages, by which Vitamin D participates in innate immune responses. The signaling pathways that involve TNF, type I IFNs and Vitamin D are inter-connected, which play critical roles in the regulation of necroptosis, apoptosis, and autophagy of the infected macrophages. This review article summarizes current knowledge about the interactions between Mtb and macrophages, focusing on cellular fates of the Mtb-infected macrophages and the regulatory molecules and cellular pathways involved in those processes.

Virulence Factors and Pathogenicity of Mycobacterium

“…Mutant of MTB in secA2 induces more apoptosis than wild type in infected macrophages, but more importantly the author shows that SodA secretion was the major SecA2 process involved in the inhibition of apoptosis [117]. Therefore, it can assume that the SecA2 secretion system, most likely through SodA, inhibits apoptosis in a mechanism probable independent of oxidative burst [118].…”

The Control of Apoptotic Death in the Cells of Granulomatous Inflammatory Lesions from Mice with Latent Tuberculous Infection in the Ex Vivo Model

“…First, pathogenic mycobacteria prevent the phagosomes containing them from merging with host cells' lysosomes and cannot thus be destroyed by lysosomal enzymes [9,[13][14][15][16][17][18]. Secondly, in infected cells, mycobacteria can modulate the expression of proinflammatory (TNFα, IFNγ, IL-1) and anti-inflammatory (IL-10) cytokines involved in the formation of cellular responses and a specific immune response of the host organism to infection [5][6][7][8][9][11][12][19][20][21]. Finally, mycobacteria cause infected cells to die either by apoptosis, which is characterized by loss of cell membrane elements, chromatin condensation, nuclear fragmentation and the formation of apoptotic bodies, or by necrosis, which is characterized Since different specific cellular responses to latent chronic and acute BCG infection in mouse cells were determined, the our aim was to analyze granulomas isolated from the lungs, spleens and bone marrow of Balb/c mice with latent BCG infection for the presence of inducers and markers of apoptotic cell death.…”

“…by compromised cell membranes and nuclear envelopes, cytoplasmic swelling and cellular breakdown [22][23][24][25]. The apoptotic death of infected macrophages has been proposed to be one of the main mechanisms by which the organism controls tuberculous infection through depopulating pathogenic microorganisms and infected cells [4][5][7][8][9]25]. By contrast, the necrotic death of infected cells leads to the release of living bacteria into the extracellular environment and further spread of infection throughout animal and human organisms [5,[24][25][26][27][28].…”

“…The apoptotic death of infected macrophages has been proposed to be one of the main mechanisms by which the organism controls tuberculous infection through depopulating pathogenic microorganisms and infected cells [4][5][7][8][9]25]. By contrast, the necrotic death of infected cells leads to the release of living bacteria into the extracellular environment and further spread of infection throughout animal and human organisms [5,[24][25][26][27][28]. At present, autophagy as a way by which host cells eliminate intracellular pathogens during latent chronic tuberculous infection and at its reactivation is extensively studied [5,8,9,23,24,29,30].…”

Análise da expressão de genes relacionados ao metabolismo do ferro em macrófagos humanos infectados com cepas de Mycobacterium tuberculosis

“…A resposta mediada por macrófagos deve ser controlada minuciosamente, pois a desregulação do mecanismo de defesa produzido por eles pode ocasionar em resposta imune exacerbada com elevada indução de citocinas proinflamatória e espécies reativas de oxigênio que danificam o tecido alvo. Já a ausência de resposta adequada e produção de moléculas anti-inflamatórias podem promover a resistência de patógenos no organismo hospedeiro o que pode levar a falha da antibioticoterapia e aumento de recorrência de doenças infecciosas e transmissibilidade (Xu et al, 2014).…”