Limited Heme Oxygenase Contribution to Modulating the Severity of Salmonella enterica serovar Typhimurium Infection

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dc.contributor.authorSebastian, Valentina P.
dc.contributor.authorMoreno-Tapia, Daniela
dc.contributor.authorMelo-Gonzalez, Felipe
dc.contributor.authorHernandez-Caceres, Maria P.
dc.contributor.authorSalazar, Geraldyne A.
dc.contributor.authorPardo-Roa, Catalina
dc.contributor.authorFarias, Monica A.
dc.contributor.authorVallejos, Omar P.
dc.contributor.authorSchultz, Barbara M.
dc.contributor.authorMorselli, Eugenia
dc.contributor.authorAlvarez-Lobos, Manuel M.
dc.contributor.authorGonzalez, Pablo A.
dc.contributor.authorKalergis, Alexis M.
dc.contributor.authorBueno, Susan M.
dc.date.accessioned2024-01-31T14:30:12Z
dc.date.available2024-01-31T14:30:12Z
dc.date.issued2022
dc.description.abstractAn important virulence trait of Salmonella enterica serovar Typhimurium (S. Typhimurium) is the ability to avoid the host immune response, generating systemic and persistent infections. Host cells play a crucial role in bacterial clearance by expressing the enzyme heme oxygenase 1 (Hmox1), which catalyzes the degradation of heme groups into Fe2+, biliverdin, and carbon monoxide (CO). The role of Hmox1 activity during S. Typhimurium infection is not clear and previous studies have shown contradictory results. We evaluated the effect of pharmacologic modulation of Hmox1 in a mouse model of acute and persistent S. Typhimurium infection by administering the Hmox1 activity inductor cobalt protoporphyrin-IX (CoPP) or inhibitor tin protoporphyrin-IX (SnPP) before infection. To evaluate the molecular mechanism involved, we measured the colocalization of S. Typhimurium and autophagosome and lysosomal markers in macrophages. Administering CoPP reduced the bacterial burden in organs of mice 5 days post-infection, while SnPP-treated mice showed bacterial loads similar to vehicle-treated mice. Furthermore, CoPP reduced bacterial loads when administered after infection in macrophages in vitro and in a persistent infection model of S. Typhimurium in vivo, while tin protoporphyrin-IX (SnPP) treatment resulted in a bacterial burden similar to vehicle-treated controls. However, we did not observe significant differences in co-localization of green fluorescent protein (GFP)-labeled S. Typhimurium with the autophagic vesicles marker microtubule-associated protein 1A/1B-light chain 3 (LC3) and the lysosomal marker lysosomal-associated membrane protein 1 (LAMP-1) in macrophages treated with CoPP. Our results suggest that CoPP can enhance antimicrobial activity in response to Salmonella infection, reducing bacterial dissemination and persistence in mice, in a CO and autophagy- independent manner.
dc.description.funderAgencia Nacional de Investigacion y Desarrollo (ANID)
dc.format.extent14 páginas
dc.fuente.origenWOS
dc.identifier.doi10.3390/antiox11061040
dc.identifier.eisbn978-3-030-28856-3
dc.identifier.eissn2076-3921
dc.identifier.isbn978-3-030-28855-6
dc.identifier.issn0197-6664
dc.identifier.pubmedidMEDLINE:34910029
dc.identifier.scopusidSCOPUS_ID:70449122103
dc.identifier.urihttps://doi.org/10.3390/antiox11061040
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/81130
dc.identifier.wosidWOS:000817622900001
dc.information.autorucFacultad de Medicina; Pardo Roa, Catalina; S/I; 225251
dc.issue.numero6
dc.language.isoen
dc.nota.accesoSin adjunto
dc.pagina.final318
dc.pagina.inicio305
dc.publisherSPRINGER INTERNATIONAL PUBLISHING AG
dc.relation.ispartofSOCIAL PSYCHOLOGY OF INEQUALITY
dc.revistaSOCIAL PSYCHOLOGY OF INEQUALITY
dc.rightsregistro bibliográfico
dc.subjectS
dc.subjectTyphimurium
dc.subjectheme oxygenase 1
dc.subjectcobalt protoporphyrin-IX
dc.subjecttin protoporphyrin-IX
dc.subjectautophagosome
dc.subjectautolysosome
dc.subjectautophagy
dc.subject.ddc610
dc.subject.deweyMedicina y saludes_ES
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleLimited Heme Oxygenase Contribution to Modulating the Severity of Salmonella enterica serovar Typhimurium Infection
dc.typeartículo
dc.volumen11
sipa.codpersvinculados225251
sipa.indexWOS
sipa.trazabilidadCarga SIPA;31-01-2024
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