tetano
Editor, Senior Moderator
Microb Pathog
. 2026 Mar 19:108457.
doi: 10.1016/j.micpath.2026.108457. Online ahead of print.
Unraveling SOCS-2 as a key mediator of Beta-Coronavirus infection pathogenesis and co-infection in chronic Chagas Disease
César Luís Nascimento Barbosa[SUP] 1 [/SUP], Samuel Luiz Teixeira Porto[SUP] 2 [/SUP], Rafaela das Dores Pereira[SUP] 2 [/SUP], Natalia Fernanda de Melo Oliveira[SUP] 2 [/SUP], Mayra Fernanda Ricci[SUP] 2 [/SUP], Rayane Aparecida Nonato Rabelo[SUP] 2 [/SUP], Paulo Gaio Leite[SUP] 2 [/SUP], Fernando Bento Rodrigues Oliveira[SUP] 2 [/SUP], Isabella Constantino Rezende[SUP] 2 [/SUP], Jorge Lucas Nascimento Souza[SUP] 3 [/SUP], Raquel Ferreira[SUP] 4 [/SUP], Celso Martins Queiroz Junior[SUP] 5 [/SUP], Allysson Thiago Cramer Soares[SUP] 6 [/SUP], Angelica Thomas Vieira[SUP] 2 [/SUP], Vivian Vasconcelos Costa[SUP] 5 [/SUP], Geovanni Dantas Cassali[SUP] 7 [/SUP], Jader Dos Santos Cruz[SUP] 2 [/SUP], Remo Castro Russo[SUP] 8 [/SUP], Mauro Martins Teixeira[SUP] 9 [/SUP], Fabiana Simão Machado[SUP] 10 [/SUP]
Affiliations
COVID-19 exacerbates pre-existing comorbidities, including Chagas Disease (CD). Suppressor of Cytokine Signaling (SOCS)-2 regulates inflammation, but its role in chronic CD and Coronavirus 2 (SARS-CoV-2) virus infection is unclear. In a murine model of chronic CD and murine hepatitis virus (MHV-3) infection/co-infection, we found that SOCS-2 expression increased in wild-type target organs in all infection models. SOCS-2 knockout (SO2 KO) mice showed significant cardiac impairment, especially during co-infection, which was associated with heightened parasitism. Additionally, in the absence of SOCS-2 co-infection affect lung function is characterized by a high viral load in the lungs and is associated with an unbalanced immune response. In contrast, WT mice displayed a robust TNF response in macrophages and dendritic cells, leading to more effective viral clearance and preserved lung function. Furthermore, SOCS-2 deficiency resulted in severe intestinal damage, including greater mucosal loss and dysbiosis. In co-infection, increased parasitism in the intestine was observed in SO2 KO mice, accompanied by a higher proportion of IL-10[SUP]+[/SUP] innate and adaptive cells, and dendritic cells showed an absolute absence of TNF, along with a reduced proportion of T CD4[SUP]+[/SUP]IFN-γ[SUP]+[/SUP] and T CD4[SUP]+[/SUP]IL-17[SUP]+[/SUP] cells and lower production of these cytokines by T CD8[SUP]+[/SUP] cells in comparison to WT co-infected mice. These findings emphasize the pivotal role of SOCS-2 in modulating immune responses and mitigating disease progression in chronic CD and CD-MHV-3 co-infections.
Keywords: Beta-Coronavirus; COVID-19; Chagas disease; SOCS-2; co-infection; immunoregulation.
. 2026 Mar 19:108457.
doi: 10.1016/j.micpath.2026.108457. Online ahead of print.
Unraveling SOCS-2 as a key mediator of Beta-Coronavirus infection pathogenesis and co-infection in chronic Chagas Disease
César Luís Nascimento Barbosa[SUP] 1 [/SUP], Samuel Luiz Teixeira Porto[SUP] 2 [/SUP], Rafaela das Dores Pereira[SUP] 2 [/SUP], Natalia Fernanda de Melo Oliveira[SUP] 2 [/SUP], Mayra Fernanda Ricci[SUP] 2 [/SUP], Rayane Aparecida Nonato Rabelo[SUP] 2 [/SUP], Paulo Gaio Leite[SUP] 2 [/SUP], Fernando Bento Rodrigues Oliveira[SUP] 2 [/SUP], Isabella Constantino Rezende[SUP] 2 [/SUP], Jorge Lucas Nascimento Souza[SUP] 3 [/SUP], Raquel Ferreira[SUP] 4 [/SUP], Celso Martins Queiroz Junior[SUP] 5 [/SUP], Allysson Thiago Cramer Soares[SUP] 6 [/SUP], Angelica Thomas Vieira[SUP] 2 [/SUP], Vivian Vasconcelos Costa[SUP] 5 [/SUP], Geovanni Dantas Cassali[SUP] 7 [/SUP], Jader Dos Santos Cruz[SUP] 2 [/SUP], Remo Castro Russo[SUP] 8 [/SUP], Mauro Martins Teixeira[SUP] 9 [/SUP], Fabiana Simão Machado[SUP] 10 [/SUP]
Affiliations
- PMID: 41864365
- DOI: 10.1016/j.micpath.2026.108457
COVID-19 exacerbates pre-existing comorbidities, including Chagas Disease (CD). Suppressor of Cytokine Signaling (SOCS)-2 regulates inflammation, but its role in chronic CD and Coronavirus 2 (SARS-CoV-2) virus infection is unclear. In a murine model of chronic CD and murine hepatitis virus (MHV-3) infection/co-infection, we found that SOCS-2 expression increased in wild-type target organs in all infection models. SOCS-2 knockout (SO2 KO) mice showed significant cardiac impairment, especially during co-infection, which was associated with heightened parasitism. Additionally, in the absence of SOCS-2 co-infection affect lung function is characterized by a high viral load in the lungs and is associated with an unbalanced immune response. In contrast, WT mice displayed a robust TNF response in macrophages and dendritic cells, leading to more effective viral clearance and preserved lung function. Furthermore, SOCS-2 deficiency resulted in severe intestinal damage, including greater mucosal loss and dysbiosis. In co-infection, increased parasitism in the intestine was observed in SO2 KO mice, accompanied by a higher proportion of IL-10[SUP]+[/SUP] innate and adaptive cells, and dendritic cells showed an absolute absence of TNF, along with a reduced proportion of T CD4[SUP]+[/SUP]IFN-γ[SUP]+[/SUP] and T CD4[SUP]+[/SUP]IL-17[SUP]+[/SUP] cells and lower production of these cytokines by T CD8[SUP]+[/SUP] cells in comparison to WT co-infected mice. These findings emphasize the pivotal role of SOCS-2 in modulating immune responses and mitigating disease progression in chronic CD and CD-MHV-3 co-infections.
Keywords: Beta-Coronavirus; COVID-19; Chagas disease; SOCS-2; co-infection; immunoregulation.