Increase of cd4+cd25highfoxp3+ cells impairs in vitro human microbicidal activity against mycobacterium tuberculosis during latent and acute pulmonary tuberculosis

Lorenzzo Lyrio Stringari, Luciana Polaco Covre, Flávia Dias Coelho da Silva, Vivian Leite de Oliveira, Maria Carolina Campana, David Jamil Hadad, Moisés Palaci, Padmini Salgame, Reynaldo Dietze, Daniel Cláudio de Oliveira Gomes, Rodrigo Ribeiro-Rodrigues

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Background Regulatory T cells (Tregs) play a critical role during Mycobacterium tuberculosis (Mtb) infection, modulating host responses while neutralizing excessive inflammation. However, their impact on regulating host protective immunity is not completely understood. Here, we demonstrate that Treg cells abrogate the in vitro microbicidal activity against Mtb. Methods We evaluated the in vitro microbicidal activity of peripheral blood mononuclear cells (PBMCs) from patients with active tuberculosis (TB), individuals with latent tuberculosis infection (LTBI, TST+/IGRA+) and healthy control (HC, TST-/IGRA-) volunteers. PBMCs, depleted or not of CD4+CD25+ T-cells, were analyzed to determine frequency and influence on microbicidal activity during in vitro Mtb infection with four clinical isolates (S1, S5, R3, and R6) and one reference strain (H37Rv). Results The frequency of CD4+CD25highFoxP3+ cells were significantly higher in Mtb infected whole blood cultures from both TB patients and LTBI individuals when compared to HC. Data from CD4+CD25+ T-cells depletion demonstrate that increase of CD4+CD25highFoxP3+ is associated with an impairment of Th-1 responses and a diminished in vitro microbicidal activity of LTBI and TB groups. Conclusions Tregs restrict host anti-mycobacterial immunity during active disease and latent infection and thereby may contribute to both disease progression and pathogen persistence.

Original languageEnglish
Article numbere0009605
Number of pages16
JournalPLoS Neglected Tropical Diseases
Volume15
Issue number7
DOIs
Publication statusPublished - Jul 2021

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