Intranasal administration of Burkholderia cepacia promotes progressive acute inflammatory changes in experimental BALB/c mice
Burkholderia cepacia (B. cepacia) is an opportunistic pathogen with versatile virulence mechanisms. The pathogenesis of B.cepacia in the immunocompetent host following intranasal exposure largely remains ambiguous. Male BALB/c mice were intranasally inoculated with B. cepacia strain 20209 (1x10{square} CFU) and evaluated on days 3, 7, 14, and 21 post-infection. Histopathology of lung, liver, spleen, and kidney tissues were performed using H&E and PAS staining. Plasma cytokines were quantified using commercial multiplex assays and ELISA. Matrix metalloproteinase-2 (MMP-2) activity was assessed via gelatin zymography and metabolomic profiling by high-resolution mass spectrometry (HRMS). Histopathological analysis revealed organ-specific pathological indices such as interstitial pneumonitis, bronchitis, leukocyte infiltration, hepatic inflammation, as well as splenic hyperplasia. Similarly, MMP-2 activity revealed time-dependent modulation, reflecting dynamic proteolytic responses. Plasma and tissue IL-18 and IL-1{beta} levels demonstrated a temporal regulation, with IL-18 peaking on day 7 post-infection, while IL-1{beta} showed a biphasic expression peaking on day 3 and 14. Untargeted metabolomics revealed differential expression of lipid metabolism, and energy pathways, with higher expression of phospholipids and sphingolipids. Together, our study portrayed a physiologically relevant intranasal BALB/c model that captures both localized and systemic inflammatory responses to B. cepacia. Our findings highlight organ-specific pathologic progression and sustained inflammation providing key insights into host-pathogen interactions.