Mycobacterium tuberculosis H37Rv Strain Increases the Frequency of CD3+TCR+ Macrophages and Affects Their Phenotype, but Not Their Migration Ability.

Lucero A Ramon-Luing,Martha Torres,Norma A Téllez-Navarrete,Claudia Carranza,Yolanda Gonzalez,Karen Medina-Quero,Leslie Chavez-Galan

doi:10.3390/ijms23010329

Abstract

In mycobacterial infections, the number of cells from two newly discovered subpopulations of CD3+ myeloid cells are increased at the infection site; one type expresses the T cell receptor (CD3+TCRαβ+) and the other does not (CD3+TCRαβ−). The role of Mycobacterium tuberculosis (Mtb) virulence in generating these subpopulations and the ability of these cells to migrate remains unclear. In this study, monocyte-derived macrophages (MDMs) infected in vitro with either a virulent (H37Rv) or an avirulent (H37Ra) Mtb strain were phenotypically characterized based on three MDM phenotypes (CD3−, CD3+TCRαβ+, and CD3+TCRαβ−); then, their migration ability upon Mtb infection was evaluated. We found no differences in the frequency of CD3+ MDMs at 24 h of infection with either Mtb strain. However, H37Rv infection increased the frequency of CD3+TCRαβ+ MDMs at a multiplicity of infection of 1 and altered the expression of CD1b, CD1c, and TNF on the surface of cells from both the CD3+ MDM subpopulations; it also modified the expression of CCR2, CXCR1, and CCR7, thus affecting CCL2 and IL-8 levels. Moreover, H37Rv infection decreased the migration ability of the CD3− MDMs, but not CD3+ MDMs. These results confirm that the CD3+ macrophage subpopulations express chemokine receptors that respond to chemoattractants, facilitating cell migration. Together, these data suggest that CD3+ MDMs are a functional subpopulation involved in the immune response against Mtb.

Highlights

Because it has been demonstrated that patients receiving tumor necrosis factor (TNF) antagonists are at a higher risk of developing tuberculosis [25], we evaluated the expression of members of the TNF pathway on CD3+ monocyte-derived macrophages (MDMs) infected with virulent and avirulent Mycobacterium tuberculosis (Mtb) strains and observed differences associated with virulence
Our data show that the virulent Mtb strain, H37Rv, did not affect the frequency of the cells of the CD3+ MDM subpopulation; 24 h of infection was enough to increase the expression of TCRαβ in CD3+ MDMs
Its virulence decreased the expression of chemokine receptors on CD3+ MDMs, but not the chemokine environment, and CD3+ MDMs maintain their migration ability

Summary

Introduction

Tuberculosis (TB), an infectious disease caused by Mycobacterium tuberculosis (Mtb), remains a serious public health problem worldwide despite the efforts to eradicate it. The. World Health Organization reported that in 2021, there were 10 million TB cases and. 1.3 million deaths [1]. TB primarily affects the lungs; alveolar macrophages represent the first line of defense for the immune response against Mtb. Macrophages play essential roles in the initial recognition, processing, and presentation of antigens; they can release proinflammatory cytokines and chemokines to recruit cells to the site of infection [2,3]

Results

Discussion

Conclusion