Neutrophil autophagy during human active tuberculosis is modulated by SLAMF1

Abstract

Neutrophils infected with Mycobacterium tuberculosis (Mtb) predominate in tuberculosis patients' lungs. Neutrophils phagocytose the pathogen, but the mechanism of pathogen elimination is controversial. Macroautophagy/autophagy, a crucial mechanism for several neutrophil functions, can be modulated by immunological mediators. The costimulatory molecule SLAMF1 can act as a microbial sensor in macrophages being also able to interact with autophagy-related proteins. Here, we demonstrate for the first time that human neutrophils express SLAMF1 upon Mtb-stimulation. Furthermore, SLAMF1 was found colocalizing with LC3B + vesicles, and activation of SLAMF1 increased neutrophil autophagy induced by Mtb. Finally, tuberculosis patients' neutrophils displayed reduced levels of SLAMF1 and lower levels of autophagy against Mtb as compared to healthy controls.Altogether, these results indicate that SLAMF1 participates in neutrophil autophagy during active tuberculosis.

PGE2 Displays Immunosuppressive Effects During Human Active Tuberculosis

“…Furthermore, we next studied the effect of PGE2 on the intracellular levels of ROS in neutrophils from HD and TB patients. As previously reported, Mtb-Ag stimulation triggered ROS production 16 (Fig. 5D).…”

“…As shown in Fig. 5A, Mtb-Ag stimulation increased the surface expression of SLAMF1 on neutrophils from HD and TB patients as we previously reported 16 . In contrast, antigen stimulation augmented PD-L1 levels only on neutrophils from HD (Fig.…”

“…A direct correlation between the number of neutrophils and TB severity disease has been previously described 15,16 . Moreover, a duality between the ability of neutrophils to clear the infection and the contribution of high numbers of these cells to in ammation, disease severity and mortality has been proposed 15 .…”

“…5). Previously, we had demonstrated that SLAMF1 promotes ROS generation during Mtb-Ag stimulation of human neutrophils 16 . Nevertheless, here we did not nd a signi cant modulation of ROS production after PGE2 treatment, at least at this time point (60 min).…”

Autophagy as a Target for Drug Development Of Skin Infection Caused by Mycobacteria

“…There is a strong relationship between autophagy signals and pattern recognition receptors, such as TLR (Toll-Like Receptors) that include TLR3, TLR4, TLR5, TLR6, TLR9, and the heterodimers TLR1/2, TLR7/8 that are capable of activating autophagy in macrophages, dendritic cells, and neutrophils (56)(57)(58). This activation occurs via signaling of the adaptor proteins MyD88 (myeloid differentiation factor 88) and TRIF (TIR-domain-containing adapter-inducing interferon-b).…”