Nitric Oxide and Apoptosis Induced in Peyer´s Patches by Attenuated Strains of Salmonella enterica Serovar Enteritidis

CERQUETTI MC; GOREN N; ROPOLO A; GRASSO D; GIACOMODONATO MN; VACCARO MI

INFECTION AND IMMUNITY

American Society for Microbiology

Lugar: Washington, DC, USA.; Año: 2002 vol. 70 p. 964 - 969

0019-9567

Nitric oxide (NO) is a toxic molecule of the immune system which contributes to the control of microbial pathogens. Additional functions of NO in innate and adaptive immunity have recently been described; these functions include the modulation of the cytokine response of lymphocytes and the regulation of immune cell apoptosis. In addition to direct microbicidal actions, NO has immunoregulatory effects relevant to the control of infections. In turn, infected macrophages and macrophage-regulating lymphocytes may undergo apoptosis during infection by Salmonella spp. In this work we investigated the ability of attenuated strains of Salmonella enterica serovar Enteritidis with different protective capacities to induce intestinal inducible nitric oxide synthase (iNOS) and apoptosis in Peyer’s patches (PP) in mice. Results showed that the intestinal iNOSactivity correlated with increased apoptosis in PP. Furthermore, the ability to induce intestinal NO production and apoptosis within the first few hours after immunization seemed to correlate with the protective capacity of mutant E/1/3 of S. enterica serovar Enteritidis. It was found that nonprotective mutant C/2/2, which was unable to induce intestinal NO production, also failed to induce apoptosis in PP. Moreover, aminoguanidine treatment at the time of immunization resulted in inhibition of the NO production and apoptosis induced by protective mutant E/1/3 and completely abolished protection against challenge. These results suggest that the induction of iNOS in the intestinal mucosa by attenuated mutant E/1/3 of S. enterica serovar Enteritidis at thetime of immunization is necessary to generate a protective immune response.