Respiratory Klebsiella pneumoniae infection transiently alters neutrophil responsiveness and enhances distal allergic inflammation.

BACKGROUND: Microbial exposure at respiratory interfaces shapes host defense, but whether prior localized bacterial infection can alter innate immune responsiveness and modulate subsequent allergic inflammation at distal sites remains unclear. This study investigated the impact of prior respiratory Klebsiella pneumoniae (KP) infection on distinct models of cutaneous allergic inflammation and the contribution of neutrophils to this cross-tissue modulation. METHODS: Mice were intratracheally infected with KP subsequently subjected to passive cutaneous anaphylaxis (PCA), oxazolone-induced contact hypersensitivity, or fluorescein isothiocyanate (FITC)-induced contact hypersensitivity. Neutrophil depletion (anti-Ly6G) and adoptive transfer of bone marrow neutrophils from infected or naïve donors were performed. Neutrophil phenotype (CXCR2, CD62L) and function were assessed by flow cytometric analysis and ex vivo LPS-stimulated cytokine production (TNF-α, IL-1β, IL-6). Allergic responses were evaluated by ear swelling, vascular permeability (Evans blue), mast cell degranulation, histamine levels, and inflammatory cytokine profiles. RESULTS: At day 7 after respiratory KP infection, bacterial loads in bronchoalveolar lavage fluid and blood were nearly undetectable, whereas inflammatory cytokines, including TNF-α, IL-1β, and IL-6, remained elevated in lung tissue, bronchoalveolar lavage fluid, and serum. Bone marrow neutrophils from KP-infected mice showed altered CXCR2 and CD62L expression and produced higher levels of TNF-α, IL-1β, and IL-6 after ex vivo LPS stimulation, suggesting enhanced neutrophil responsiveness during the post-infectious phase. Prior KP infection aggravated distal allergic inflammation in the PCA and oxazolone models, as shown by increased ear swelling, Evans blue extravasation, mast cell degranulation, histamine production, neutrophil infiltration, and inflammatory mediator expression. In contrast, the additional effect of KP infection was more limited in the FITC-induced contact hypersensitivity model, indicating a model-dependent response. In the PCA model, neutrophil depletion attenuated KP-enhanced allergic inflammation, whereas adoptive transfer of neutrophils from KP-infected donors restored and enhanced PCA responses more strongly than transfer of control neutrophils. CONCLUSION: Respiratory KP infection is associated with post-infectious neutrophil priming and enhanced distal allergic inflammation in a model-dependent manner. These findings suggest that prior bacterial respiratory infection may influence subsequent allergic responses through altered neutrophil responsiveness, with effects that are context-dependent rather than universal across all hypersensitivity models.