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

Daniel P Gail; Vinicius G Suzart; Weinan Du; Avinaash Kaur Sandhu; Jessica Jarvela; Mary Nantongo; Ivan Mwebaza; Soumya Panigrahi; Michael L Freeman; David H Canaday; W Henry Boom; Richard F Silver; Stephen M Carpenter

doi:10.1016/j.isci.2023.107706

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

iScience. 2023 Aug 23;26(9):107706. doi: 10.1016/j.isci.2023.107706. eCollection 2023 Sep 15.

Authors

Daniel P Gail¹, Vinicius G Suzart^{1

2}, Weinan Du¹, Avinaash Kaur Sandhu^{1

2}, Jessica Jarvela^{3

4}, Mary Nantongo², Ivan Mwebaza^{1

2}, Soumya Panigrahi¹, Michael L Freeman^{1

2}, David H Canaday^{1

4}, W Henry Boom^{1

2

5}, Richard F Silver^{3

4}, Stephen M Carpenter^{1

2

5}

Affiliations

¹ Division of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
² Biomedical Sciences Training Program, Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
³ Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
⁴ Department of Medicine, The Louis Stokes Cleveland V.A. Medical Center, Cleveland, OH 44106, USA.
⁵ Division of Infectious Diseases and HIV Medicine, Department of Medicine, University Hospitals Cleveland Medical Center, Cleveland, OH 44139, USA.

Abstract

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.

Keywords: Immune response; Immunology; Microbiology.

Abstract

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