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. 2023 Jul 10;14:983299. doi: 10.3389/fmicb.2023.983299

FIGURE 1.

FIGURE 1

Mycobacterial uptake by neutrophils and interaction partners during infection. Neutrophils recognize and phagocytose the mycobacterium leading to successive events that include different immune cell types. (1, 2) After M.tb is engulfed, direct lysis includes NADPH oxidase starting to generate ROS which initiates granule degradation and subsequent release of NE. Neutrophils also release lysosomal enzymes and human neutrophil peptides lysing the mycobacterium. Bacteria that resist the direct oxidative killing will then be targeted by indirect antimicrobial effects that may involve the cooperation between different cell types. (3) Necrosis of neutrophils is dependent on ROS and ESAT-6. Removal of necrotic neutrophils by macrophages enhances M.tb replication and dissemination by inducing necrosis in macrophages. Activated macrophages can also form extracellular traps which can trap the microbe and prevent its further action on the host. METs are formed in an ESX-1-dependent manner mediated by levels of IFN-γ and involving the subsequent release of IL-8, thus activating neutrophils. (4) When inhibiting ROS and neutrophil necrosis, neutrophils may also undergo apoptosis restoring the ability of macrophages to control M.tb growth. (5) DCs can internalize pathogen antigens through apoptotic neutrophils cross-presenting them to T lymphocytes driving a protective Th1 response with subsequent release of IFN-γ and TNF-α, thus contributing to the maintenance of granuloma with IFN-γ avoiding excessive infiltration of neutrophils. (6) Additionally, neutrophils may participate by recruiting T cells via CXCR3-signaling chemokines. (7) For NETs to be formed upon M.tb infection, phagocytosis by neutrophils is essential. In the process of neutrophil activation, Hsp72 is released and NETs are formed. Elastase contained in NETs can activate macrophages and increase their capacity to kill the mycobacterium. Phagocytosis of apoptotic infected neutrophils and NETs by macrophages leads to the secretion of cytokines that signal other innate and adaptive immune cells for the elimination of the prevailing infection. Created with BioRender.com.