Chronic administration of the antidepressant fluoxetine impact on Yersinia enterocolitica oral infection and reactive arthritis development in TNFR1 deficient mice

SAMANTA CELESTE FUNES; JUAN EDUARDO SILVA ; MARÍA SILVIA DI GENARO

Congreso; LXIX REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INMUNOLOGÍA (SAI); 2021

Fluoxetine (FLX) is a selective serotonin reuptake inhibitor (SSRIs)with antidepressant and immunomodulatory effects. Whether FLXtreatment impacts gastrointestinal bacterial infections and their sequelae, such as Reactive arthritis (ReA), remains unknown. We investigated the FLX effect on Yersinia enterocolitica (Ye) O:3 infectionand ReA in a TNFR1 knockout mouse model. Differences in maleand female mice were also evaluated. Male and female TNFR1 KOmice were orally infected with Ye O:3 (1-5x108 colony-forming units).From infection day, FLX (20 mg/kg/day) or water (control) was administrated in drinking water. On day 5, the number CFU was determined in stool, spleen, and mesenteric lymphoid nodes. The weight,mobility, mortality, and arthritis score of the mice were recorded. Onday 21, splenic dendritic cells (DCs) infiltration and their maturationmarkers were evaluated by flow cytometry in surviving mice. Wefound that male TNFR1 KO mice have lower survival and higherclinical score after Ye infection. On day 5, FLX treatment increasedbacterial dissemination in males. Surviving mice developed ReA butfemales treated with FLX showed greater severity than controls.Furthermore, FLX mice showed a lower proportion of splenic DCswithout changing in CD86 expression. We conclude that TNFR1KO male mice are more susceptible than females to Ye infection.The modulatory effect of FLX hinders more the immune responseof males increasing systemic bacterial spread. Finally, the chronicadministration of FLX did not reduce the severity of ReA and, in contrast, increased it in females. Although DCs infiltration in the spleenwas reduced, the expression CD86 marker did not change, so weinfer that the increased arthritis severity could be related to defective DCs migration. The results contribute to understanding howantidepressant chronic treatment influences the immune responsesagainst pathogens and the maintenance of immune homeostasis.