Where Ideas grow

Immune Regulation

ABOUT

The immune system has evolved several regulatory mechanisms to achieve maximum protection in the absence of pathology. Pathogens have co-evolved strategies to evade the host immune response. The Immune Regulation group is dedicated to the understanding of the mechanisms explored by hosts and pathogens to modulate the immune response and of the events leading to disease when this regulation fails.

 

RESEARCH

On the host side, we study the anti-inflammatory cytokine IL-10. As this molecule has attracted much attention for potential clinical applications, understanding the molecular mechanisms underlying both IL-10 expression and IL-10 action in immune cells is critical for a better and safer manipulation of the immune system. Our recent data revealed a role for IL-10 in hematopoiesis, by promoting myelopoiesis, and in accelerating aging-related features. We have evidence that IL-10 is accelerating cellular senescence and are pursuing these findings further.

On the pathogen side, we investigate how Mycobacterium tuberculosis, a pathogen that kills over 1.5 million people per year, interacts with the host immune system. We are exploring the physiopathology of tuberculosis in a novel, integrative way, by bringing together the host, the pathogen and the environment diversity. We center our efforts in unveiling the molecular bases implicated in the induction of variable inflammatory responses by M. tuberculosis clinical isolates in different hosts and how these strategies of immune regulation can be explored towards the host benefit. We also investigate how perturbations on the host status (as imposed by comorbidities such as diabetes and cancer) impact on the immune interactions with M. tuberculosis.

Our collaborative network included different groups within i3S, clinicians, and research teams at the Pasteur Institute (Paris), the Francis Crick Institute (London), the Swiss Tropical and Public Health Institute (Basel) and the Biomedicine Institute (Valencia).

 

Chronic IL-10 exposure leads to a disorganized spleen structure.

Selected Publications

Cardoso A., Castro A., Martins A., Carriche G., Murigneux V., Castro I., Cumano A., Vieira P., Saraiva M.,
The Dynamics Of Interleukin-10-afforded protection during dextran sulfate sodium-induced colitis. Frontiers in Immunology9(MAR):, 2018. [Journal: Article] [CI: 3] [IF: 4,7]
DOI: 10.3389/fimmu.2018.00400 SCOPUS: 85042686207. .

Lobo-Silva D., Carriche G., Castro A., Roque S., Saraiva M.,
Interferon-ß regulates the production of IL-10 by toll-like receptor-activated microglia. GLIA65(9):1439-1451, 2017. [Journal: Article] [CI: 4] [IF: 5,8]
DOI: 10.1002/glia.23172 SCOPUS: 85021258982. .

Bastos H., Osório N., Castro A., Ramos A., Carvalho T., Meira L., Araújo D., Almeida L., Boaventura R., Fragata P., Chaves C., Costa P., Portela M., Ferreira I., Magalhães S., Rodrigues F., Sarmento-Castro R., Duarte R., Guimarães J., Saraiva M.,
A prediction rule to stratify mortality risk of patients with pulmonary tuberculosis. PLoS ONE11(9):, 2016. [Journal: Article] [CI: 7] [IF: 2,8]
DOI: 10.1371/journal.pone.0162797 SCOPUS: 84992386220. .

Moreira-Teixeira L., Sousa J., McNab F., Torrado E., Cardoso F., Machado H., Castro F., Cardoso V., Gaifem J., Wu X., Appelberg R., Castro A., O'Garra A., Saraiva M.,
Type i IFN inhibits alternative macrophage activation during mycobacterium tuberculosis infection and leads to enhanced protection in the absence of IFN-γ signaling. Journal of Immunology197(12):4714-4726, 2016. [Journal: Article] [CI: 27] [IF: 4,9]
DOI: 10.4049/jimmunol.1600584 SCOPUS: 85002328285. .

Cruz A., Ludovico P., Torrado E., Gama J., Sousa J., Gaifem J., Appelberg R., Rodrigues F., Cooper A., Pedrosa J., Saraiva M., Castro A.,
IL-17A promotes intracellular growth of Mycobacterium by inhibiting apoptosis of infected macrophages. Frontiers in Immunology6(SEP):, 2015. [Journal: Article] [CI: 4] [IF: 5,7]
DOI: 10.3389/fimmu.2015.00498 SCOPUS: 84946550863. .

Cardoso F., Castro F., Moreira-Teixeira L., Sousa J., Torrado E., Silvestre R., Castro A., Saraiva M., Pais T.,
Myeloid sirtuin 2 expression does not impact long-term Mycobacterium tuberculosis control. PLoS ONE10(7):, 2015. [Journal: Article] [CI: 7] [IF: 3,1]
DOI: 10.1371/journal.pone.0131904 SCOPUS: 84940426429. .

Teixeira-Coelho M., Guedes J., Ferreirinha P., Howes A., Pedrosa J., Rodrigues F., Lai W., Blackshear P., O'Garra A., Castro A., Saraiva M.,
Differential post-transcriptional regulation of IL-10 by TLR2 and TLR4-activated macrophages. European Journal of Immunology44(3):856-866, 2014. [Journal: Article] [CI: 19] [IF: 4]
DOI: 10.1002/eji.201343734 SCOPUS: 84896030127. .

Carmona J., Cruz A., Moreira-Teixeira L., Sousa C., Sousa J., Osorio N., Saraiva A., Svenson S., Kallenius G., Pedrosa J., Rodrigues F., Castro A., Saraiva M.,
Mycobacterium tuberculosis Strains Are Differentially Recognized by TLRs with an Impact on the Immune Response. PLoS ONE8(6):, 2013. [Journal: Article] [CI: 39] [IF: 3,5]
DOI: 10.1371/journal.pone.0067277 SCOPUS: 84879468975. .

Bastos H., Osório N., Gagneux S., Comas I., Saraiva M.,
The troika host-pathogen-extrinsic factors in tuberculosis: Modulating inflammation and clinical outcomes. Frontiers in Immunology8(JAN):, 2018. [Journal: Review] [CI: 3] [IF: 4,7]
DOI: 10.3389/fimmu.2017.01948 SCOPUS: 85042558392. .

Lobo-Silva D., Carriche G., Castro A., Roque S., Saraiva M.,
Balancing the immune response in the brain: IL-10 and its regulation. Journal of Neuroinflammation13(1):, 2016. [Journal: Review] [CI: 66] [IF: 5,1]
DOI: 10.1186/s12974-016-0763-8 SCOPUS: 84997106994. .