Mycobacterium tuberculosis impairs human memory CD4+ T cell recognition of M2 but not M1-like macrophages

• Published in: iScience Vol. 26; no. 9; p. 107706
• Main Authors: Gail, Daniel P., Suzart, Vinicius G., Du, Weinan, Kaur Sandhu, Avinaash, Jarvela, Jessica, Nantongo, Mary, Mwebaza, Ivan, Panigrahi, Soumya, Freeman, Michael L., Canaday, David H., Boom, W. Henry, Silver, Richard F., Carpenter, Stephen M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.09.2023; Elsevier
• Subjects: Immune response; Immunology; Microbiology; Microbiology; Immunology; Immune response
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2023.107706

Direct recognition of Mycobacterium tuberculosis (Mtb)-infected cells is required for protection by CD4+ T cells. While impaired T cell recognition of Mtb-infected macrophages was demonstrated in mice, data are lacking for humans. Using T cells and monocyte-derived macrophages (MDMs) from individuals with latent Mtb infection (LTBI), we quantified the frequency of memory CD4+ T cell activation in response to autologous MDMs infected with virulent Mtb. We observed robust T cell activation in response to Mtb infection of M1-like macrophages differentiated using GM-CSF, while M2-like macrophages differentiated using M-CSF were poorly recognized. However, non-infected GM-CSF and M-CSF MDMs loaded with exogenous antigens elicited similar CD4+ T cell activation. IL-10 was preferentially secreted by infected M-CSF MDMs, and neutralization improved T cell activation. These results suggest that preferential infection of macrophages with an M2-like phenotype limits T cell-mediated protection against Mtb. Vaccine development should focus on T cell recognition of Mtb-infected macrophages. [Display omitted] •Human memory CD4+ T cells recognize Mtb-infected M1 but not M2-like macrophages•Both macrophage subsets activate CD4+ T cells when loaded with inactivated Mtb•IL-10 is preferentially expressed by Mtb-infected M2-like (M-CSF) macrophages•IL-10 neutralization augments T cell recognition of infected M2-like macrophages Immunology; Immune response; Microbiology