CLOSTRIDIOIDES DIFFICILE INFECTION IN ARGENTINA: FROM EPIDEMIOLOGY TO IMMUNE PROTECTION MECHANISMS

BARBERO, AM; PALMA, S; MORICONI, ND; ERBITI, G; ALTAMIRANDA, C; CALVO ZARLENGA, M; MACHAIN, M; BALBI, MG; SUAREZ, J; HERNANDEZ DEL PINO, RE; PASQUINELLI, V

San Luis

Congreso; LXXI REUNIÓN CIENTÍFICA ANUAL DE LA SOCIEDAD ARGENTINA DE INMUNOLOGÍA (SAI); 2023

SOCIEDAD ARGENTINA DE INMUNOLOGÍA (SAI)

Clostridioides difficile infection (CDI) is one of the most common health-careassociated infection implicated in 15–25% of antibiotic-associated diarrheaepisodes. C. difficile is a Gram+, obligate anaerobic and spore-forming bacteriumthat is widespread in the environment and has been identified by the CDC as anurgent antimicrobial resistance threat. The very few reports about the prevalenceof CDI in Argentina, the low awareness and inconsistent diagnostic andsurveillance protocols suggest that this infection is markedly underestimated. Itis imperative to have a deeper knowledge of CDI epidemiology and the intricateinterplay between C. difficile microbial factors and the host immune system. Weanalyzed 168 samples from hospitalized individuals with diarrhea in aretrospective study. We found a prevalence of CDI of 23,81% by using analgorithm that includes EIA, PCR and toxigenic culture. Through a meta-analysisthat compares our results with 39 publications, no factors commonly associatedwith CDI were found as risk predictors in our study cohort. Parametersencompassing leukocyte, neutrophil, monocyte, lymphocyte, basophile, andplatelet counts were established as predictors of CDI risk. We are also currentlystudying the immune response against C. difficile. We showed that bothmacrophages and platelets interact with C. difficile. Macrophages can internalizeC. difficile by macropinocytosis and platelets improve this uptake. Our findingsare the first evidence for the internalization of vegetative C. difficile by humanmacrophages and highlight the role of platelets in innate immunity during CDI.Furthermore, using an in vivo model of CDI, we observed that C. difficilemodulates T cell functions. IL-17 is tightly regulated trough the course of infection.The decrease on IL-17 production and the increase of IL-10 could be associatedwith disease resolution. Moreover, we found a CD4-CD8- IL-17 producingpopulation in lamina propria, which needs further exploration. Finally, CDItreatment in Argentina is based on oral administration of metronidazole orvancomycin. Failure rate of existing antibiotics in combating C. difficile seems tobe high and increasing, and recurrent CDI is frequently observed. Alternativetherapeutic approaches are undoubtedly needed. Aloe Vera (AV) has been usedas an immunomodulatory and antimicrobial agent in the treatment of diseases.Interestingly, AV gel inhibits C. difficile growth and significantly increasesvancomycin´s effect. On the other hand, we also evaluated the role of AV as aprotector agent of the intestinal epithelia. AV has a protective effect on themonolayer’s integrity treated with C. difficile (BI/NAP1/027) strain or TcdA/TcdBtoxins. This first evidence positions AV as a potential promising combinationtherapy against C. difficile, reducing the antibiotics concentration treatment andthe detrimental consequences on the commensal microbiota, protecting theepithelial barrier integrity.