Innate Immunity Holding the Flanks until Reinforced by Adaptive Immunity against Mycobacterium tuberculosis Infection

Abstract

T cells play a cardinal role in imparting protection against Mycobacterium tuberculosis (Mtb). However, ample time is required before T-cells are able to evoke efficient effector responses in the lung, where the mycobacterium inflicts disease. This delay in T cells priming, which is termed as lag phase, provides sufficient time for Mtb to replicate and establish itself within the host. In contrast, innate immunity efficiently curb the growth of Mtb during initial phase of infection through several mechanisms. Pathogen recognition by innate cells rapidly triggers a cascade of events, such as apoptosis, autophagy, inflammasome formation and nitric oxide production to kill intracellular pathogens. Furthermore, bactericidal mechanisms such as autophagy and apoptosis, augment the antigen processing and presentation, thereby contributing substantially to the induction of adaptive immunity. This manuscript highlights the role of innate immune mechanisms in restricting the survival of Mtb during lag phase. Finally, this article provides new insight for designing immuno-therapies by targeting innate immune mechanisms to achieve optimum immune response to cure TB.

The use of Phyllanthus niruri L. as an immunomodulator for the treatment of infectious diseases in clinical settings

“…In the process of mycobacterial infection control, the role of TNF-α seems to be more primordial. The cytokine is mainly secreted by monocytes, activated macrophages, T-lymphocytes, and dendritic cells, and acts in synergy with IFN-γ, upon various kinds of cells, to induce the production of reactive nitrogen intermediates and mediate the tuberculostatic function of macrophages [50,51]. TNF-α stimulates the immune cell migration to the infection site, contributing to the granuloma formation capable of controlling the disease progression.Induction of apoptosis is also associated with the control of M. tuberculosis by TNF-α.…”

Innate immunity in tuberculosis: host defense vs pathogen evasion

“…3 These receptors are also involved in the initiation of various innate immune defense-associated cellular functions, such as phagocytosis, autophagy, apoptosis and inflammasome activation. 4,5 Mtb is an extremely successful intracellular pathogen that has co-evolved with its host for eons. The host immune cells are triggered into a non-sterilizing control of Mtb, which causes a latent Mtb infection that maintains equilibrium between the host and the pathogen via granuloma formation.…”

Human lung ex vivo infection models

“…In 2012, around 9.0 million people developed tuberculosis (TB) and 1.5 million people died of this chronic infectious lung disease (Zumla et al 2013). Although the innate immune system may clear early infection of M. tuberculosis in a significant number of cases (Khan et al 2016;Morrison et al 2008), little is known about the initial interaction of this important pathogen with human lung tissue. Ganbat et al (2016) have now started to explore such interactions by establishing an ex vivo human lung infect i o n m o d e l w i t h v a r i o u s m y c o b a c t e r i a l s t r a i n s (M. tuberculosis, M. abscessus, M. avium).…”