Increased Susceptibility of IgA-Deficient Mice to Pulmonary Francisella tularensis Live Vaccine Strain Infection

Abstract

Francisella tularensis, the causative agent of tularemia, is most deadly in the pneumonic form; therefore, mucosal immunity is an important first line of defense against this pathogen. We have now evaluated the lethality of primary F. tularensis live vaccine strain (LVS) pulmonary infection in mice that are defective in IgA (IgA ؊/؊ mice), the predominant mucosal Ig isotype. The results showed that IgA ؊/؊ mice were more susceptible than IgA ؉/؉ mice to intranasal F. tularensis LVS infection, despite developing higher levels of LVS-specific total, IgG, and IgM antibodies in the bronchoalveolar lavage specimens following infection. In addition, the absence of IgA resulted in a significant increase in bacterial loads and reduced survival. Interestingly, IgA

Role of Interleukin-12 in Protection against Pulmonary Infection with Methicillin-Resistant Staphylococcus aureus

“…Administration of IL-12 enhanced production of IFN-␥ by NK (12,28,29). Our data also demonstrated the critical role of IFN-␥ in IL-12-mediated protection against pulmonary MRSA.…”

B cell subsets are activated and produce cytokines during early phases of Francisella tularensis LVS infection

“…Moreover, serum antibodies have been seen to be capable of conferring protection against lethal respiratory LVS challenge when administered therapeutically up to 48 h post-exposure [15]. This role of antibodies has been documented further by data from IgAdeficient mice that were highly susceptible to primary pulmonary LVS infection [16] and were unable to survive lethal challenge after vaccination [17]. The experiments with IgA À/-mice, moreover, provide examples of the cross-talk among the B cells (and/or their products) and other immunocompetent cells.…”

“…The experiments with IgA À/-mice, moreover, provide examples of the cross-talk among the B cells (and/or their products) and other immunocompetent cells. Moreover, IgA À/-mice were observed to have in particular decreased numbers of IFN-g-secreting CD4 þ and CD8 þ T cells in the lung on day 9 postinfection, lower pulmonary IFN-g levels, and, at early time points, reduced levels of IL-12 [16].…”

Enhanced differentiation of intraepithelial lymphocytes in the intestine of polymeric immunoglobulin receptor‐deficient mice

“…After the cells were treated with haemolytic buffer (0Á144 M NH 4 Cl/ 0Á017 M Tris-HCl, pH 7Á65), the remaining cells were incubated with a cocktail of biotinylated anti-CD3, biotinylated anti-B220, biotinylated anti-CD11b and biotinylated antiCD11c mAbs (all from BD Biosciences), followed by incubation with streptavidin microbeads. The cells were magnetically separated using an LS column and the passingthrough cells were collected.…”

“…1 It is reported that sIgA binds viral antigens penetrating across the epithelial layers and effectively protects the host against pathogenic microorganisms in naive mice. [2][3][4] On the other hand, after IgA À/À mice and J-chain À/À mice, both of which are deficient in sIgA, have been immunized by pathogenic microorganisms, they exhibit resistance to mucosal infection by the same pathogens. [5][6][7][8] These findings indicate that sIgA plays a critical role for neutralizing and inactivating microorganisms in the mucous layer of the naive host and is not necessarily required for the guard against pathogenic infection in the host where specific immunity has already been established.…”