Distinct Strategies Employed by Dendritic Cells and Macrophages in RestrictingMycobacterium tuberculosisInfection: Different Philosophies but Same Desire

Abstract

Dendritic cells (DCs) and macrophages (Mϕs) are professional antigen-presenting cells (APCs) that can efficiently phagocytose Mycobacterium tuberculosis (Mtb), the etiological agent of tuberculosis (TB). It is quite interesting to mention here that DCs and Mϕs use distinct strategies to combat and eliminate Mtb. Similarly, Mtb employs different mechanisms to counteract the action of DCs and Mϕs. Mϕs are evolved with specialized, innate, defensive machinery to restrict growth of Mtb at the initial phase of infection. However, DCs are more endowed toward initiating adaptive immunity by activating naïve T cells. During encounter with Mtb, DCs and Mϕs deliver discrete functions via triggering through different pattern recognition receptors (PRRs) expressed by these APCs. Mtb-infected DCs and Mϕs show differential expression of genes encoding cytokines, chemokines, costimulatory molecules, and adhesion molecules. Interestingly, Mtb impairs the immune defensive machinery by exploiting various PRRs. Remarkably, selective signaling through PRRs by Mtb abrogates the bactericidal activity of Mϕs, but subverts differentiation of monocytes to DCs. In this article, we highlight the role of PRRs in inducing distinct immune response by DCs and Mϕs against Mtb. Concurrently, we also discuss smart strategies exploited by Mtb to impair the function of host DCs and Mϕs.

Immune Response to Mycobacterium tuberculosis: A Narrative Review

“…DCs are functionally located in the middle between innate and adaptive immunity. These cells play a fundamental role in the immune defense system due to antigen presentation, co-stimulating activity and the large cytokine production capacity with activity on the lymphocytes cluster of differentiation (CD) 4 (32). DCs role in TB immunity is controversial.…”

Aggregation state of Mycobacterium tuberculosis impacts host immunity and augments pulmonary disease pathology

“…These studies support our finding that Mtb-AG can cause severe inflammation and host cell destruction, resulting in larger, necrotic granulomas in infected rabbit lungs. Phagocytes, such as macrophages, dendritic cells (DC), and neutrophils, may utilize various phagocytic mechanisms to engulf Mtb 22,23 . For example, macrophages employ different modes of phagocytosis through Fc and C3 receptors, as reported earlier 23,24 .…”

Impact of selective immune-cell depletion on growth of Mycobacterium tuberculosis (Mtb) in a whole-blood bactericidal activity (WBA) assay

“…Whilst neutrophils may act to control early infection through antigen presentation and the ensuing initiation of adaptive immunity, neutrophils undergo necrotic cell death brought about by virulent Mtb infection, are phagocytosed by macrophages, and it has previously been shown in a whole blood model that it is this presence of necrotic neutrophilic debris (as opposed to intact neutrophils) which propagate and enhance Mtb replication [9, 10, 12]. CD11c+ DCs, having differentiated from inflammatory circulating monocytes, have been shown to enter the lung parenchyma where they acquire then transport intact Mtb to draining lymph nodes, where they have a well-established role in initiating adaptive immunity [13–15]. The corollary of this study’s finding of increased Mtb growth in the absence of myeloid (CD11c+) DCs is that DCs in whole blood result in the reduced survival of Mtb.…”