Macrophages and control of granulomatous inflammation in tuberculosis

Abstract

The granuloma that forms in response to Mycobacterium tuberculosis must be carefully balanced in terms of immune responses to provide sufficient immune cell activation to inhibit the growth of the bacilli, yet modulate the inflammation to prevent pathology. There are likely many scenarios by which this balance can be reached, given the complexity of the immune responses induced by M. tuberculosis. In this review, we focus on the key role of the macrophage in balancing inflammation in the granuloma.

Figure 1

Balance of responses in the granuloma dictate bacterial control and pathology. There are a variety of combinations that can lead to an inflammatory granuloma in active tuberculosis (TB). Three possibilities are shown: (a) Active granuloma with high bacterial numbers, many classically activated macrophages (CAMs) and alternatively activated macrophages (AAMs), T helper 1 (TH1) cells, some neutrophils, and few regulatory T cells (Tregs). (b) Active granuloma with too many Tregs, AAMs, not enough TH1 and CAMs, high neutrophils, and high bacterial load. (c) Active granuloma with fewer bacilli, but overabundance of CAMs and TH1 cells, and not enough Tregs. Two possible latent granulomas are shown, although there are likely many combinations. (d) Latent granuloma with CAMs and AAMs in balance, with relatively few T cells. (e) Latent granuloma with more Tregs to balance the higher TH17 and TH1, but a balance of AAMs and CAMs.