Reinforcing the Functionality of Mononuclear Phagocyte System to Control Tuberculosis

Abstract

The mononuclear phagocyte system (MPS) constitutes dendritic cells, monocytes, and macrophages. This system contributes to various functions that are essential for maintaining homeostasis, activation of innate immunity, and bridging it with the adaptive immunity. Consequently, MPS is highly important in bolstering immunity against the pathogens. However, MPS is the frontline cells in destroying Mycobacterium tuberculosis (Mtb), yet the bacterium prefers to reside in the hostile environment of macrophages. Therefore, it may be very interesting to study the struggle between Mtb and MPS to understand the outcome of the disease. In an event when MPS predominates Mtb, the host remains protected. By contrast, the situation becomes devastating when the pathogen tames and tunes the host MPS, which ultimately culminates into tuberculosis (TB). Hence, it becomes extremely crucial to reinvigorate MPS functionality to overwhelm Mtb and eliminate it. In this article, we discuss the strategies to bolster the function of MPS by exploiting the molecules associated with the innate immunity and highlight the mechanisms involved to overcome the Mtb-induced suppression of host immunity. In future, such approaches may provide an insight to develop immunotherapeutics to treat TB.

Infection of Monocytes From Tuberculosis Patients With Two Virulent Clinical Isolates of Mycobacterium tuberculosis Induces Alterations in Myeloid Effector Functions

“…Nevertheless, inflammatory monocytes can also play a deleterious effect by fueling and perpetuating the inflammatory response leading to unrestricted control of microbial infection and tissue pathology (Shi and Pamer, 2011;Pahari et al, 2018;Sampath et al, 2018). Our group and others have reported phenotypic and functional alterations in monocytes from TB patients compared to healthy controls (Sanchez et al, 2006;Balboa et al, 2011;Castaño et al, 2011a,b;Lastrucci et al, 2015).…”

“…Monocytes have been described as playing a dual role during Mtb infection. They are essential in the anti-mycobacterial defense through innate activation mechanisms and triggering the acquired immunity against Mtb; however, they may also participate in pathogen dissemination, inflammatory reaction, and the tissue damage occurring during TB (Pahari et al, 2018). It has reported that circulating monocytes from patients with pulmonary tuberculosis (TB) exhibit phenotypic and functional alterations compared with healthy controls (Sanchez et al, 2006;Castaño et al, 2011a;Chavez-Galan et al, 2015), which can be associated with disease progression or severity.…”

Mycobacterium tuberculosis host cell interaction: Role of latency associated protein Acr-1 in differential modulation of macrophages

“…Macrophages play a pivotal role in the activation as well as differentiation of naïve CD4 T cells [ 2 , 7 ]. Next, we explored the ability of AcrMΦpre and AcrMΦpost treated macrophages to activate T cells.…”

“…It is of paramount importance to comprehend the intricate host–pathogen interaction and the evasion approaches thrived by M . tb to circumvent immune onslaught of the host [ 2 , 7 ]. The pathogen systematically deteriorates the immune function of the host by down-modulating overall activities and functioning of both macrophage and DC cell population [ 8 ].…”

“…In general, antigen presenting cells including MΦs participate in a pivotal role in suppressing immunity against M . tb and facilitate differentiation of naïve T cells to effector cells [ 2 , 7 , 16 , 17 ]. The invading pathogen in turn modulates host immune machinery that leads to induction of tolerance that otherwise eventually help its safe survival inside the host [ 7 ].…”