Multi-modal molecular profiling of the host response in pneumonia

Pneumonia and sepsis represent complex syndromes in which heterogeneity in the host immune response plays a decisive role in disease severity, progression, complications, and mortality. This thesis investigates the molecular architecture of the host response in community-acquired pneumonia and sepsis, with the aim of identifying biologically meaningful patterns that may inform future precision immunomodulatory strategies.
The thesis is organized into three interconnected parts. Part I focuses on platelets as immune effector cells, examining platelet function, metabolism, and protein release to better understand their contribution to inflammation, coagulation, and host defense. Part II addresses myeloid immune responses by profiling neutrophils and monocytes using proteomic and lipidomic approaches with particular attention to metabolic reprogramming alongside inflammatory and stress-related pathways. Part III expands the scope to the systemic level by characterizing plasma lipidomic responses in sepsis due to community-acquired pneumonia, providing insight into organism-wide immune–metabolic alterations.
Across all parts, integrative analytical strategies, including advanced statistical methods and multi-omics approaches, are employed to capture molecular heterogeneity and relate host response patterns to clinical trajectories. By focusing on coordinated immune–metabolic processes, this thesis highlights recurrent and potentially interconnected perturbations across multiple cell types, offering a conceptual framework for stratified, host response–driven immunomodulatory strategies in pneumonia and sepsis