T cell-specific P2RX7 favors lung parenchymal CD4+ T cell accumulation in response to severe lung infections
Igor Santiago-Carvalho,
Gislane Almeida-Santos,
Bruna Gois Macedo,
Caio Cesar Barbosa-Bomfim,
Fabricio Moreira Almeida,
Marcos Vinícios Pinheiro Cione,
Trupti Vardam-Kaur,
Mia Masuda,
Sarah Van Dijk,
Bruno Marcel Melo,
Rogério Silva do Nascimento,
Rebeka da Conceição Souza,
Alba Lucínia Peixoto-Rangel,
Robson Coutinho-Silva,
Mario Hiroyuki Hirata,
José Carlos Alves-Filho,
José Maria Álvarez,
Elena Lassounskaia,
Henrique Borges da Silva,
Maria Regina D’Império-Lima
Affiliations
Igor Santiago-Carvalho
Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-000, Brazil; Department of Immunology, Mayo Clinic, Scottsdale, AZ 85259, USA
Gislane Almeida-Santos
Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-000, Brazil
Bruna Gois Macedo
Department of Immunology, Mayo Clinic, Scottsdale, AZ 85259, USA
Caio Cesar Barbosa-Bomfim
Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-000, Brazil
Fabricio Moreira Almeida
Laboratory of Biology of Recognition, North Fluminense State University, Campos, RJ 28013-602, Brazil
Marcos Vinícios Pinheiro Cione
Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-000, Brazil
Trupti Vardam-Kaur
Department of Immunology, Mayo Clinic, Scottsdale, AZ 85259, USA
Mia Masuda
Department of Immunology, Mayo Clinic, Scottsdale, AZ 85259, USA
Sarah Van Dijk
Department of Immunology, Mayo Clinic, Scottsdale, AZ 85259, USA
Bruno Marcel Melo
Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP 14040-900, Brazil
Rogério Silva do Nascimento
Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-000, Brazil
Rebeka da Conceição Souza
Laboratory of Biology of Recognition, North Fluminense State University, Campos, RJ 28013-602, Brazil
Alba Lucínia Peixoto-Rangel
Laboratory of Biology of Recognition, North Fluminense State University, Campos, RJ 28013-602, Brazil
Robson Coutinho-Silva
Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21941-902, Brazil
Mario Hiroyuki Hirata
Department of Clinical and Toxicological Analysis, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, SP 05508-000, Brazil
José Carlos Alves-Filho
Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP 14040-900, Brazil
José Maria Álvarez
Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-000, Brazil
Elena Lassounskaia
Laboratory of Biology of Recognition, North Fluminense State University, Campos, RJ 28013-602, Brazil
Henrique Borges da Silva
Department of Immunology, Mayo Clinic, Scottsdale, AZ 85259, USA; Corresponding author
Maria Regina D’Império-Lima
Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-000, Brazil; Corresponding author
Summary: CD4+ T cells are key components of the immune response during lung infections and can mediate protection against tuberculosis (TB) or influenza. However, CD4+ T cells can also promote lung pathology during these infections, making it unclear how these cells control such discrepant effects. Using mouse models of hypervirulent TB and influenza, we observe that exaggerated accumulation of parenchymal CD4+ T cells promotes lung damage. Low numbers of lung CD4+ T cells, in contrast, are sufficient to protect against hypervirulent TB. In both situations, lung CD4+ T cell accumulation is mediated by CD4+ T cell-specific expression of the extracellular ATP (eATP) receptor P2RX7. P2RX7 upregulation in lung CD4+ T cells promotes expression of the chemokine receptor CXCR3, favoring parenchymal CD4+ T cell accumulation. Our findings suggest that direct sensing of lung eATP by CD4+ T cells is critical to induce tissue CD4+ T cell accumulation and pathology during lung infections.
