How Mycobacterium tuberculosis subverts host immune responses

Abstract

Mycobacterium tuberculosis is the causative agent of pulmonary tuberculosis which has infected one third of the mankind and causes 2-3 million deaths worldwide each year. The persistence of the infection ensues from the ability of M. tuberculosis to subvert host immune responses in favor of survival and growth of mycobacteria in macrophages. The mechanisms by which M. tuberculosis manipulates the host immune system have only recently come to light. These activities are attributed to lipoarabinomannans (LAM) and their precursors lipomannans (LM), two predominant glycolipids of M. tuberculosis cell wall. LM are able to skew anti-mycobacterial immune responses into un-protective ones, while LAM evoke immunosupression upon binding to macrophage and dendritic cell receptors specialized in binding to "self" host components. A newly emerging idea implicates plasma membrane rafts in LM and LAM signaling. Depending on acylation patterns, the glycolipids may either directly incorporate into the raft membrane via mannosylphosphatidylinositol anchors or interact with raft-associated proteins to affect the assembly of receptor signaling complexes.

Endocytosis of Mycobacterium tuberculosis Heat Shock Protein 60 Is Required to Induce Interleukin-10 Production in Macrophages*

“…For example, in macrophages interaction of a synthetic lipopeptide Pam 3 CSK 4 with TLR2 induced a pro-inflammatory response (86), whereas PPE18, a mycobacterial TLR2 ligand, induced production of anti-inflammatory IL-10 response (38). Interestingly, signaling through TLR4 predominantly triggers production of pro-inflammatory cytokines that favor Th1 lineage commitment (87,88). Similar to the Mtbhsp60, other mammalian and microbial HSP60s were also found to require functional TLR4 on macrophages and dendritic cells for pro-inflammatory activity (27,48,89,90).…”

Bacterial immunostat: Mycobacterium tuberculosis lipids and their role in the host immune response

“…On the other hand, LAM inhibits IL-12 production by human dendritic cells and modulates M. tuberculosis-induced macrophage apoptosis 53 . Man-LAM mimics a mammalian cell mannose receptor, which enables M. tuberculosis to evade host defense mechanisms, inhibiting phagosome maturation by suppressing the production of IL-12 and TNF and increasing IL-10 production by dendritic cells or monocytic cells 54 . Dao et al 52 postulated that the LM: LAM ratio in the mycobacterial cell wall can directly affect the virulence of M. tuberculosis and the outcome of an infection.…”

Src Homology 3-interacting Domain of Rv1917c of Mycobacterium tuberculosis Induces Selective Maturation of Human Dendritic Cells by Regulating PI3K-MAPK-NF-κB Signaling and Drives Th2 Immune Responses

“…In contrast, Th2 cells that secrete IL-4, IL-5, IL-9, and IL-13 are critical for antibody class switching in B cells as well for inducing a humoral response (7)(8)(9)(10). Th2-driven immunity is significantly efficient in the eradication of extracellular pathogens but markedly deficient in clearing intracellular infections, including pathogenic mycobacteria.…”