Mycobacterium Tuberculosis Infection and Inflammation: what is Beneficial for the Host and for the Bacterium?

Abstract

Tuberculosis is still a major health problem in the world. Initial interactions between Mycobacterium tuberculosis and the host mark the pathway of infection and the subsequent host inflammatory response. This inflammatory response is tightly regulated by both the host and the bacterium during different stages of infection. As infection progresses, the initial intense pro-inflammatory response observed is regulated by suppressive mediators balancing inflammation. In this environment, M. tuberculosis battles to survive interfering with the host inflammatory response. In this review we discuss the major effector molecules involved in inflammation in relation to the different stages of M. tuberculosis infection.

Keywords: Mycobacterium tuberculosis; inflammation; pattern recognition receptors; tuberculosis.

Figure 1

Granuloma formation. Schematics of lesion structure at each stage of granuloma formation in immunocompetent (A) or immunodeficient (B) M.tb-infected people. Once M.tb reaches the lungs, bacilli are internalized by AMs triggering the subsequent inflammatory response. In the early stage, the granuloma has a core of infected macrophages enclosed by mononuclear phagocytes, surrounded by lymphocytes. In the case of immunocompetent people, infection will be contained within small and compact granulomas characterized by the presence of a large number of IFN-γ CD4 T cells. For immunodeficient people, as the granuloma matures, it is characterized by being rich in activated macrophages and with few surrounding lymphocytes. Over time the granuloma caseous necrotic center liquefies and cavitates, spilling thousands of infectious M.tb bacilli into the airways. (C–F) Schematic of granulomas developed in the absence or presence of the main inflammatory mediators described in M.tb pathogenesis.

Figure 2

Antigen presenting cell receptors involved in M. tb infection. M.tb cell wall components associate with a subset of immune receptors initiating phagocytosis and mediating specific host cell responses. Interactions with certain receptors or soluble collectins lead to the activation of pro-/anti-inflammatory responses in the host that may influence the intracellular survival of M.tb. TLR, Toll-like receptor; MR, mannose receptor; DC-SIGN, dendritic cell-specific intercellular adhesion molecule-3 grabbing non-integrin; CR, complement receptor; SP-A and SP-D, surfactant protein-A and -D; MBL, mannose binding lectin; Dectin-1, dendritic cell-associated C-type lectin-1; Mincle, macrophage-inducible C-type lectin; NOD-2, nucleotide-binding oligomerization domain-like receptor 2.