Who benefits from granulomas, mycobacteria or host?

Abstract

By investigating host-pathogen interactions in zebrafish using intravital imaging, Davis and Ramakrishnan (2009) provide evidence that aggregates of immune cells known as granulomas, long thought to constrain mycobacterial infection, may instead facilitate its spread.

Figure 1. Stages of Granuloma Formation in Tuberculosis

Findings by Davis and Ramakrishnan (2009) explain the initial stage of tuberculosis, which is characterized by expansion of the bacterial population in the absence of adaptive immunity. Bacterial multiplication and spread are facilitated by formation of the nascent granuloma. Infected macrophages undergo apoptosis and recruit uninfected macrophages to the site. These recruited macrophages phagocytose the remnants of infected cells and their bacterial contents. Some newly infected macrophages egress to seed secondary granuloma formation. When initiation of adaptive immunity eventually occurs, CD4⁺ and CD8⁺ effector T lymphocytes are recruited to infected tissue and curtail bacterial growth. Although essential for control of the infection, adaptive immunity cannot eradicate it. The mature granuloma represents an equilibrium between virulent mycobacteria and the host immune response.