The effect of iNOS inhibition on the protection induced by an attenuated mutant of Salmonella enteritidis

GIACOMODONATO MN, GOREN NB, AND CERQUETTI MC.

Orlando, USA

Congreso; 101st General Meeting of American Society for Microbiology; 2001

American Society for Microbiology

Pathogenic enteric microorganisms like Salmonella spp. induce the expression of pro inflammatory molecules including TNF-alpha and nitric oxide. Initially, this early inflammatory response may contribute to protection from injury as well as repair after injury occurs. In addition to direct microbicidal actions, reactive nitrogen intermediates have immunoregulatory effects relevant to the control of infection. In this work, we investigated the effect of inducible nitric oxide synthase (iNOS) inhibition at the time of immunization on the protection induced by mutant E/1/3 of S. enteritidis. Balb/c mice received two oral doses (109 CFU/mouse) of the vaccine strain a week apart, and they were challenged 14 days after the last immunizing dose. Mice received two ip injections of aminoguanidina (AG) or dexamethasone (DXM) before each immunization. The challenge dose was 104 CFU/mouse of the virulent strain of S. enteritidis. NOS activity was determinated in the gut by measuring the production of 14C citrulline from 14C arginine.  Animals treated with AG or DXM and immunized with E/1/3 mutant showed NOS activity similar to that of the control mice (262 + 18; 313 + 47; and 265 + 77 pmol/g respectively). Vaccinated mice inoculated only with the mutant E/1/3 showed significantly higher activity of NOS (706 + 25 pmol/g) compared to that control or treated groups (p<0.01). Seventy two % of the control mice died within 12 days after challenge, whereas the survival rate of immunized animals reached 62 %. Interestingly, the survival rate of mice treated with the wild type strain of S. enteritidis was 75 % and 100 %, respectively. Our results suggest that inhibition of iNOS activity at the time of immunization could improve the protection induced by live attenuated vaccine strains of S. enteritidis.