Host-Pathogen Interaction Mechanisms in Aspergillus fumigatus Invasive Infection of Immunocompromised Patients in Lagos University Teaching Hospital: A Transcriptome-Immunoproteomics Study

Invasive pulmonary aspergillosis (IPA) caused by Aspergillus fumigatus is a devastating opportunistic infection in immunocompromised patients with case fatality rates exceeding 50 percent in resource-limited settings where early diagnosis is challenging. The molecular host-pathogen interaction mechanisms governing IPA pathogenesis in Nigerian patient populations have not been investigated. This study combined dual-transcriptomics and host immunoproteomics to characterize host-pathogen interaction mechanisms during IPA in immunocompromised patients at Lagos University Teaching Hospital (LUTH), Lagos State, South West Nigeria. Bronchoalveolar lavage (BAL) samples from 30 confirmed IPA cases and 30 non-IPA immunocompromised controls were processed for dual RNA-sequencing (simultaneous human and fungal transcriptomics) and serum immunoproteomics by 2D-DIGE combined with LCMS protein identification. A. fumigatus strains were isolated from BAL and genome-sequenced for virulence gene context. Results revealed significant upregulation of A. fumigatus secondary metabolite biosynthesis clusters (including gliotoxin and fumagillin) in clinical isolates compared to laboratory reference strains. Host transcriptomics demonstrated suppression of Th17 immune pathways and paradoxical NF-kB hyperactivation in IPA patients. Immunoproteomics identified six novel differentially expressed host proteins as candidate IPA biomarkers, including calprotectin and chitinase-3-like protein 1. An integrated host-pathogen interaction network model was constructed, identifying galectin-3 as a hub node mediating immune-fungal crosstalk. These findings provide original mechanistic insight into IPA pathogenesis in a Nigerian clinical context and generate diagnostic biomarker candidates for future validation. Keywords: Aspergillus fumigatus, invasive aspergillosis, transcriptomics, immunoproteomics, host-pathogen interaction.