Frontiers in Immunology (Jul 2022)
IL-10 Overexpression After BCG Vaccination Does Not Impair Control of Mycobacterium tuberculosis Infection
- Catarina M. Ferreira,
- Catarina M. Ferreira,
- Consuelo Micheli,
- Consuelo Micheli,
- Palmira Barreira-Silva,
- Palmira Barreira-Silva,
- Ana Margarida Barbosa,
- Ana Margarida Barbosa,
- Mariana Resende,
- Mariana Resende,
- Mariana Resende,
- Manuel Vilanova,
- Manuel Vilanova,
- Manuel Vilanova,
- Ricardo Silvestre,
- Ricardo Silvestre,
- Cristina Cunha,
- Cristina Cunha,
- Agostinho Carvalho,
- Agostinho Carvalho,
- Fernando Rodrigues,
- Fernando Rodrigues,
- Margarida Correia-Neves,
- Margarida Correia-Neves,
- Margarida Correia-Neves,
- António Gil Castro,
- António Gil Castro,
- Egídio Torrado,
- Egídio Torrado
Affiliations
- Catarina M. Ferreira
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal
- Catarina M. Ferreira
- ICVS/3B’s - PT Government Associate Laboratory, Braga/Guimarães, Portugal
- Consuelo Micheli
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal
- Consuelo Micheli
- ICVS/3B’s - PT Government Associate Laboratory, Braga/Guimarães, Portugal
- Palmira Barreira-Silva
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal
- Palmira Barreira-Silva
- ICVS/3B’s - PT Government Associate Laboratory, Braga/Guimarães, Portugal
- Ana Margarida Barbosa
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal
- Ana Margarida Barbosa
- ICVS/3B’s - PT Government Associate Laboratory, Braga/Guimarães, Portugal
- Mariana Resende
- Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Porto, Portugal
- Mariana Resende
- Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto, Porto, Portugal
- Mariana Resende
- Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto (ICBAS-UP), Porto, Portugal
- Manuel Vilanova
- Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Porto, Portugal
- Manuel Vilanova
- Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto, Porto, Portugal
- Manuel Vilanova
- Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto (ICBAS-UP), Porto, Portugal
- Ricardo Silvestre
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal
- Ricardo Silvestre
- ICVS/3B’s - PT Government Associate Laboratory, Braga/Guimarães, Portugal
- Cristina Cunha
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal
- Cristina Cunha
- ICVS/3B’s - PT Government Associate Laboratory, Braga/Guimarães, Portugal
- Agostinho Carvalho
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal
- Agostinho Carvalho
- ICVS/3B’s - PT Government Associate Laboratory, Braga/Guimarães, Portugal
- Fernando Rodrigues
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal
- Fernando Rodrigues
- ICVS/3B’s - PT Government Associate Laboratory, Braga/Guimarães, Portugal
- Margarida Correia-Neves
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal
- Margarida Correia-Neves
- ICVS/3B’s - PT Government Associate Laboratory, Braga/Guimarães, Portugal
- Margarida Correia-Neves
- Division of Infectious Diseases, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
- António Gil Castro
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal
- António Gil Castro
- ICVS/3B’s - PT Government Associate Laboratory, Braga/Guimarães, Portugal
- Egídio Torrado
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal
- Egídio Torrado
- ICVS/3B’s - PT Government Associate Laboratory, Braga/Guimarães, Portugal
- DOI
- https://doi.org/10.3389/fimmu.2022.946181
- Journal volume & issue
-
Vol. 13
Abstract
Control of tuberculosis depends on the rapid expression of protective CD4+ T-cell responses in the Mycobacterium tuberculosis (Mtb)-infected lungs. We have recently shown that the immunomodulatory cytokine IL-10 acts intrinsically in CD4+ T cells and impairs their parenchymal migratory capacity, thereby preventing control of Mtb infection. Herein, we show that IL-10 overexpression does not impact the protection conferred by the established memory CD4+ T-cell response, as BCG-vaccinated mice overexpressing IL-10 only during Mtb infection display an accelerated, BCG-induced, Ag85b-specific CD4+ T-cell response and control Mtb infection. However, IL-10 inhibits the migration of recently activated ESAT-6-specific CD4+ T cells into the lung parenchyma and impairs the development of ectopic lymphoid structures associated with reduced expression of the chemokine receptors CXCR5 and CCR7. Together, our data support a role for BCG vaccination in preventing the immunosuppressive effects of IL-10 in the fast progression of Mtb infection and may provide valuable insights on the mechanisms contributing to the variable efficacy of BCG vaccination.
Keywords
