Intranasal immunization with recombinant outer membrane protein A induces protective immune response against Stenotrophomonas maltophilia infection

Abstract

Stenotrophomonas maltophilia ( S . maltophilia ), a multi-drug resistant opportunistic pathogen, is associated with nosocomial and community-acquired infections. Preventive and therapeutic strategies for such infections are greatly needed. In this study, sequence alignment analysis revealed that Outer membrane protein A (OmpA) was highly conserved among S . maltophilia strains but shared no significant similarity with human and mouse proteomes. In mice, intranasal immunization with S . maltophilia recombinant OmpA (rOmpA) without additional adjuvant induced sustained mucosal and systemic rOmpA-specific antibody responses. Treatment with rOmpA stimulated significantly higher levels of secretion of IFN-γ, IL-2, and IL-17A (All P <0.05) from the primary splenocytes isolated from rOmpA-immunized mice than from the primary splenocytes isolated from PBS-immunized mice. Furthermore, mice immunized with rOmpA showed significantly reduced bacterial burden in the lung and reduced levels of pro-inflammatory cytokines (TNF-α and IL-6) in bronchoalveolar lavage fluid (BALF) 24 hours after intranasal S . maltophilia infection, indicating that immunization with rOmpA may have protective effects against S . maltophilia challenge in mice. Our findings suggest that intranasal immunization with rOmpA may induce mucosal and systemic immune responses in mice, trigger Th1- and Th17-mediated cellular immune responses, and thus stimulate host immune defense against S . maltophilia infection. These results also demonstrate that intranasal vaccination may offer an alternative approach to current strategies since it induces a mucosal as well as a systemic immune response.

Yeast cell-wall polysaccharides improve immunity and attenuate inflammatory response via modulating gut microbiota in LPS-challenged laying hens

“…In LPS challenged birds, LEfSe highlights the greater differential abundances of several opportunistic pathogens, including Corynebacteriaceae (Corynebacterium), Staphylococcaceae (Staphylococcus), Erysipelotrichaceae, Brevundimonas and Stenotrophomonas. All of them have been documented to be associated with inflammatory infections [66][67][68][69][70]. In the current study, correlation analysis revealed positive associations between Corynebacteriaceae (Corynebacterium) and Staphylococcaceae (Staphylococcus) with ileal TLR4 and/or IL-6 expressions.…”

Stenotrophomonas maltophilia outer membrane protein A induces epithelial cell apoptosis via mitochondrial pathways

“…DAPI was purchased from Beyotime Biotechnology. Purified His-tagged recombinant S. maltophilia OmpW (rOmpW) and rabbit anti-rOmpA serum were obtained from the previous study (Xu et al, 2018;Li et al, 2019). Bax (sc-20067), Bcl-xL (sc-136207), cytochrome c (sc-13156), AIF (sc-55519), caspase-3 (sc-7272), PARP (sc-53643), and β-actin (sc-81178) antibodies were purchased from Santa Cruz.…”

“…We developed the His-tagged rOmpA in our previous study (Xu et al, 2018;Li et al, 2019). The recombinant plasmid expressing S. maltophilia K279a OmpA was transformed into E. coli BL21, which was cultured and induced by IPTG.…”

“…Recently, it has been reported that the prevalence of S. maltophilia infection in intensive care units has been increasing continuously (Chang et al, 2012). Outer membrane protein A (OmpA) is a unique protein on the surface or embedded in the cell membrane of Gram-negative bacteria and is closely associated with the development of bacterial infection and the activation of host immune response (March et al, 2011;Li et al, 2019). Previous studies have suggested that the pathogenicity of S. maltophilia may be associated with OmpA-medicated adhesion to the host cells and the consequent stimulation of host cell apoptosis (Gaddy et al, 2009;Zhang et al, 2010).…”