BRUCELLA INFECTION AFFECTS FUNCTIONALITY OF DECIDUA STROMAL CELLS AND TROPHOBLASTS

ZAVATTIERI, L; MACCHI, R; MUÑOZ GONZALEZ, F; CANELLADA, AM; FERRERO, MC; BALDI, PC

San Luis

Congreso; LXXI Reunión Científica Anual de la Sociedad Argentina de Inmunología SAI; 2023

Sociedad Argentina de Inmunología

The ability of trophoblasts to migrate, form tubes and invade the decidua isessential for a successful pregnancy. These processes are modulated bycytokines produced by decidual cells. Brucella infections are associated withreproductive complications in humans and animals. We evaluated if Brucella canimpair functions of decidual cells and trophoblasts that are relevant for asuccessful pregnancy. The effect of Brucella infection on trophoblast migrationwas evaluated with the scratch test using the human trophoblastic cell lineSwan71. Wound closure was significantly diminished in trophoblasts infected withB. abortus (Multiplicity of Infection 50: 45%; MI 500: 36% vs. 83% in uninfectedcontrols), and similar results were observed with Brucella suis and Brucellamelitensis infections. Human endometrial stromal cells (THESC) were infectedwith different Brucella species (B. abortus, B. suis, or B. melitensis) before or afterdecidualization with medroxyprogesterone and cAMP, and conditioned media(CM) were used to stimulate Swan71 cells during the scratch test. Wound closurewas reduced in Swan71 cells treated with CM from B. abortus-infecteddecidualized THESC as compared to uninfected CM (20% vs. 86%). Similarly,wound closure was inhibited by CM obtained from THESC cells infected beforedecidualization (8.5% vs. 72.8%). Comparable results were observed with theother strains. Inflammatory signals are known to affect or impact trophoblastfunctions. Trophoblast migration (wound closure) improved when CM from B.abortus-infected THESC at different MI was treated with neutralizing antibodies(Ab) against CXCL8 or CCL2 chemokines before addition to the scratch test.Incubation with CM plus anti-IL-8 antibody increased wound closure by 59 and45 % for MI 50 and 500 respectively vs. CM untreated, while, anti-CCL2 antibodytreatment increased 55% and 52% for MI 50 and 500 respectively. Moreover,trophoblast tube formation assay was more successful in uninfected controls (NI)being reduced in the presence of infected THESC CM, as revealed by the numberof master junctions (NI: 88; MI 50: 33; MI 500: 19), master segments (NI:152; MI50: 28; MI 500: 46.5 and meshes (NI:56; MOI 50: 16; MOI 50: 20; MOI 500:13.5).In addition, when THESC were infected, the attachment area of trophoblastspheroids (invasion) was affected (NI:0.98; MOI 50: 0.71; MOI 250: 0.53; MOI500: 0.47). Overall, the normal function of trophoblasts and decidual cells, andcross-talk between them, can be affected by Brucella infection.