Microbial Offense vs Host Defense: Who Controls the TB Granuloma?

Abstract

The granuloma is the hallmark of tuberculosis and simultaneously signifies acquisition of an infection and induction of a host immune response. But who benefits more from the development of the granuloma, the host or the pathogen? Is microbe or man dictating disease course and progression? Mycobacterial diseases affect humans and animals alike, and the concepts presented in this review reflect host-pathogen interactions that influence not only mycobacterial granulomas in humans and animals but also other infectious granulomatous diseases that are encountered in veterinary medicine. Current dogma supports that an organized granuloma is a mark of an adequate and "restrictive" host immune response. However, the formation of a granuloma also provides a niche for the maturation, growth, and persistence of numerous infectious agents, and these pathogens devote some portion of their genetic machinery to ensuring these structures' form. An understanding of pathogens' contributions to granuloma formation can aid the development of host-directed therapies and other antimicrobial and antiparasitic therapies that can tip this balance in favor of a restrictive host response and elimination-not just containment-of the infectious organism. This review discusses animal models that have aided our understanding of pathogens' contribution to the host response and how mycobacterial virulence genes direct host pathology in ways that may aid disease transmission and/or persistence in the form of latent infection.

Immune Response to Mycobacterium tuberculosis: A Narrative Review

“…This switch is caused by ESAT-6 (60), a well-known Mtb virulence factor involved in the ESX secretion system, to which it gives its name. ESAT-6 causes the transformation of MΦ from phenotype M1, which produces IL-6, IL-12 and TNF-α, into MΦ with phenotype M2, which is capable of stimulating production of IL-10 (60, 61, 70). As currently known, IL-6 and TNF-α favor inflammation, whilst IL-10 curbs it.…”

Animal Models of Tuberculosis Vaccine Research: An Important Component in the Fight against Tuberculosis

“…, and is widely used as an animal model in vaccine research owing to its advantages of small size, easy reproduction, and low cost [36]. A er infection by M. marinum, both adult zebrafish and larvae can form granulomas that are very similar to those observed in humans, and the innate and adaptive immune responses elicited against mycobacteria are composed of the same primary components found in humans [37][38][39]. In addition, the transparent characteristic of zebrafish larvae is also suitable for fluorescence imaging.…”

Multinucleated Giant Cell Formation as a Portal to Chronic Bacterial Infections

“…The granuloma is a critical structure that has the dual role of containment and safe environment for the pathogen. The factors that influence the outcome of infection are not fully characterized, but it is thought that uncontrolled replication and an imbalance between pro- and anti-inflammatory mediators aids the bacteria to escape containment and result in active TB [ 33 , 34 ]. If the balance is right, the bacteria are contained, and the infection remains asymptomatic with the formation of mature granulomas containing dormant bacteria.…”