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

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.