FN-plays a detrimental role in murine defense against nasal colonization of taphylococcus aureus ara

The anterior nares are the major reservoir in humans of Staphylococcus aureus with the risk of developing endogenous infections or transmitting infections to susceptible persons. The mechanisms that mediate attachment of staphylococci to the nasal mucosa are little known. The purpose of the present work was to study some factors that could influence the nasal colonization in an animal model of mice. We investigated the possible role of IFN. We used S. aureus ATCC 35556 (SA113) slime-producing and ATCC 25923 nonslime-producing strains. Male 6-week-old BALB/c, C57BL/6 (wild-type, WT), and gene-deficient IL-12p40 (IL-12p40−/−) or IL-4 (IL-4−/−) mice on C57BL/6 background were infected with a dose of S. aureus of 106 CFU in 10 l of saline. The total number of S. aureus CFU per nose and lung, specific IgA response and IFNlevels were evaluated. Significant higher CFU were recovery from the narines of C57BL/6 compared with BALB/c mice either after ATCC 35556 (p < 0.0001) and ATCC 25923 (p < 0.02) strain infection. Low IgA response correlated with high bacterial counting in the C57BL/6 nasal region. Moreover, C57BL/6 mice showed major colonization of slime-producing S. aureus ATCC 35556 than non-slime-producing ATCC 25923 S. aureus strain (p < 0.02). IL-12p40−/−mice clarified the bacteria from their nose more efficiently that WT mice after slime-producing S. aureus (p < 0.0001). Accordingly, significant lower level of IFNwere detected in IL-12p40−/− compared with WT mice after infection with this strain (p < 0.03). The results suggested the influence of the slime production in nasal colonization of S. aureus, and indicate at first time that IFNmay play a detrimental role in this mucosal infection. These results could contribute to elucidate mucosal immune mechanisms involved in S. aureus colonization and then control infections in susceptible persons. Staphylococcus aureus is known to be part of the normal skin and ucosal microflora. The anterior nares are the major reservoir in umans of this opportunistic pathogen with the risk of developing ndogenous infections or transmitting infections to susceptible perons [1]. The mechanisms that mediate attachment of staphylococci o the nasal mucosa are little known. Colonization is a multifactorial rocess that requires a variety of adaptive mechanisms including utrient acquisition, adherence to host tissues, and evasion of, or rotection against host defenses [2,3]. S. aureus produces a myriad f virulence factors that contribute to its ability to cause disease. ell wall components such as peptidoglycan, teichoic acids, and apsule, as well as adhesins, proteases, exoproteins, and exotoxns, all promote the virulence of this pathogen [4]. Certain S. aureus trains have the ability to develop highly consolidated structure: the ∗ Corresponding author at: Laboratorio de Inmunopatología, Area Microbiología, niversidad Nacional de San Luis, Chacabuco y Pedernera, 5700 San Luis, Argentina. el. : +54 2652 423789; fax: +54 2652 431301. E-mail address: sdigena@unsl.edu. ar (M.S. Di Genaro). 165-2478/$ – see front matter © 2009 Elsevier B.V. All rights reserved. oi:10.1016/j.imlet. 2009.03. 003 © 2009 Elsevier B.V. All rights reserved. biofilm, which is believed to make the organisms more resistant to antibiotics and host defenses [5]. Formation of the biofilm requires polysaccharidic intercellular adhesine (PIA), which is synthesized by enzymes encoded by the intercellular adhesion cluster (ica) [6]. Although numerous animal models have contributed to the knowledge of virulence factors involved in staphylococcal infection, only a few reported studies have examined the interactions of S. aureus with the nasal mucosa in an animal model [2,7]. An important aspect of the host innate immune response to S. aureus is opsono phagocytic killing by polymorphonuclear leukocytes (PMNs). The essential role of phagocytic killing in host clearance of S. aureus is apparent because patients who are neutropenic or have defects in PMN function suffer recurrent staphylococcal infections. In contrast, little information is available on how various T cell populations influence the outcome of staphylococcal infections. It is known that S. aureus and its products induce various cytokines that play beneficial and detrimental roles in hosts exposed to these bacterial infections [8,9]. The purpose of the present work was to study some factors that could influence the nasal colonization in an animal model in mice. We 1 logy Letters 123 (2009) 185–188