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Mycobacterium tuberculosis resisters despite HIV exhibit activated T cells and macrophages in their pulmonary alveoli. | LitMetric

AI Article Synopsis

  • - To investigate natural resistance to infection, researchers studied PLWH in a high-transmission area, focusing on alveolar leukocytes' role by analyzing bronchoalveolar lavage cells through single-cell RNA-sequencing of samples from both LTBI positive and TST negative individuals.
  • - Resisters showed an increased presence of M1 phenotype alveolar macrophages and significant alveolar lymphocytosis, with 5 out of 6 exhibiting higher numbers of CD4 and CD8 T cells compared to LTBI individuals.
  • - The study found that poly-cytotoxic CD8 T cells, which expressed mycobactericidal granulysin and key activating receptors, were significantly more abundant in the alveoli of resisters, highlighting their

Article Abstract

To understand natural resistance to ( ) infection, we studied people living with HIV (PLWH) in an area of high transmission. Given that alveolar leukocytes may contribute to this resistance, we performed single cell RNA-sequencing of bronchoalveolar lavage cells, unstimulated or stimulated with . We obtained high quality cells for 7 participants who were TST & IGRA positive (called LTBI) and 6 who were persistently TST & IGRA negative (called resisters). Alveolar macrophages (AM) from resisters displayed more of an M1 phenotype relative to LTBI AM at baseline. Alveolar lymphocytosis (10%-60%) was exhibited by 5/6 resisters, resulting in higher numbers of CD4 and CD8 -expressing cells at baseline and upon challenge than LTBI samples. Mycobactericidal granulysin was expressed almost exclusively by a cluster of CD8 T cells that co-expressed granzyme B, perforin and NK cell receptors. For resisters, these poly-cytotoxic T cells over-represented activating NK cell receptors and were present at 15-fold higher numbers in alveoli compared to LTBI. Altogether, our results showed that alveolar lymphocytosis, with increased numbers of alveolar -expressing cells and CD8 poly-cytotoxic T cells, as well as activated AM were strongly associated with protection from persistent infection in PLWH.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10863035PMC
http://dx.doi.org/10.21203/rs.3.rs-3889020/v1DOI Listing

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