Macrophage heterogeneity and plasticity in tuberculosis

Abstract

Macrophages are the primary host cells for Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), during its intracellular survival in humans. The pathogen has a remarkable capacity to survive within the hostile environment of macrophages. However, primary infection does not result in active TB disease in most individuals. The majority of individuals remain latently infected, wherein the bacteria are held in check by the host immune response. Nevertheless, such individuals can develop active TB later upon the decline in their immune status. In contrast, in a small fraction of infected individuals, the host immune response fails to control the growth of M. tuberculosis bacilli, and granulomatous TB develops progressively. Elucidating the molecular and phenotypic events that govern the outcome of the infection within macrophages is fundamental to understanding the key features of these cells that could be equally critical in infection control. The molecular details of the M. tuberculosis‐macrophage interaction continue to be discerned, and emerging evidence suggests that macrophage population that participate in infection is heterogeneous. While the local environment and developmental origin could influence the phenotypic heterogeneity and functional plasticity of macrophages, M. tuberculosis has also been demonstrated to modulate the polarization of macrophages. In this review, we draw on work investigating specialized macrophage populations and their interactions with M. tuberculosis with respect to pathogenesis and specific immune responses. Understanding the mechanisms that control the repertoire of macrophage phenotypes and behaviors during infection may provide prospects for novel TB control strategies through modulation of immunobiological functions of macrophages.

Modelling Bovine Granuloma Formation In Vitro upon Infection with Mycobacterium Avium Subspecies Paratuberculosis

“…M1 polarization primes macrophages for a variety of pro-inflammatory cell-mediated responses, among them granuloma formation. M2 polarization, meanwhile, accompanies humoral immunity, is favored by IL-10 stimulation, and redirects uninfected MDMs from granuloma formation to wound repair [65]. GLCCs formed under conditions favoring M2 polarization more closely model activation of latent Map than they do the early stages of latency, while the latter is what we aim to simulate.…”

Chemokine Receptors and Phagocyte Biology in Zebrafish

“…Macrophages are crucial players of the inflammatory response triggered by tissue damage and exhibit remarkable phenotypic plasticity (51,54). Live tracking of fluorescently labeled macrophages in zebrafish showed that these cells are recruited to injury shortly after neutrophils at early stages [several papers].…”

Clinical Significance of M1/M2 Macrophages and Related Cytokines in Patients with Spinal Tuberculosis

“…The M.tb infection is regulated by both immune and pathogenic factors [15,16]. The research on the body immunity mainly focuses on the regulation of various cytokines on tuberculous granulomas and the function and type of T cells in the development of tuberculous granulomas.…”