Effect of Hemoxigenase 1 induction in the severity of Salmonella enterica serovar Typhimurium infection in mice

Sebastian, V; Salazar, G; Pardo-Roa, C; Salazar-Echegarai, FJ; Schultz, B; Vallejo, O; Alvarez-Lobos, M; Kalergis, MA; Bueno, SM

Abstract

Salmonella enterica is the leading cause of infectious gastroenteritis and systemic diseases in humans. The main virulence trait of Salmonella enterica serovar Typhimurium (S. Typhimurium) is the ability to avoid the immune response of the host. The specific factors that participate in the ability of S. Typhimurium to avoid immune response are not totally elucidated. One of the immunomodulatory molecules expressed by the host that has a role in bacterial clearance is Heme oxygenase 1 (HO-1). HO-1 is an enzyme that catalyzes the heme degradation reaction that releases Fe3+, biliverdin and carbon monoxide (CO). The role of HO-1 production during S. Typhimurium infection is not clear and previous studies show contradictory results. In this study we proposed to induce HO-1 expression in mice prior to infection with S. Typhimurium. To achieve this, we treated C57BL/6 mice with Cobalt Protoporphyrin (CoPP), an inducer of HO-1 expression, and after 24 h mice were infected with S. Typhimurium. Weight change, clinical score and survival were measured daily. After 5 days of infection we determined bacterial loads in spleen, liver, feces, blood and mesenteric lymph nodes. Our results show that infected and CoPP-treated mice showed a tendency to survive more than infected-untreated mice, and to decrease bacterial load at 5 days post- infection in spleen, liver and feces. Interestingly, bacterial load in blood of infected and CoPP-treated mice was higher than in infected and untreated mice. Our results suggest that HO-1 plays an important role in S. Typhimurium clearance and dissemination to deeper tissues in mice.

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Fecha de publicación: 2017