Molecular Mechanisms of Host–Pathogen Interactions in Pneumonia

Pneumonia, a leading cause of global morbidity and mortality, continues to pose significant clinical and public health challenges, particularly amid the escalating threat of antimicrobial resistance. Advances in molecular bacterial pathogenesis have revealed that disease outcomes are governed by complex molecular dialogues between bacterial pathogens and the host’s immune system. Pathogens employ an array of specialized virulence factors—including adhesins, secretion systems, and immune-modulatory toxins—to evade immune surveillance, breach epithelial barriers, and establish infection.

In response, the host mounts multilayered defense programs involving pattern recognition receptors, inflammasomes, the complement system, and tissue-repair pathways to control infection and restore homeostasis. The complement cascade serves as a critical component of innate immunity by mediating bacterial opsonization, recruiting inflammatory cells, and promoting pathogen lysis. Beyond its antimicrobial activity, complement signaling modulates cytokine responses and shapes adaptive immunity. However, many respiratory pathogens have evolved mechanisms to subvert or exploit complement pathways—such as binding host complement regulators or degrading complement proteins—enhancing their persistence and virulence within the host.

Recent advances in single-cell transcriptomics, spatial omics, and in situ imaging have begun to illuminate the dynamic and spatially organized nature of host–pathogen interactions within infected lung tissues. Yet, substantial gaps remain in understanding how these molecular exchanges drive pathogen adaptation, immune dysregulation, and clinical heterogeneity across pneumonia cases.

This Research Topic aims to advance our mechanistic understanding of bacterial pneumonia by uncovering how virulence traits interface with, modify, or circumvent host immune responses—and how these interactions shape disease progression and patient outcomes. We encourage submissions that integrate cutting-edge approaches, including high-throughput omics, genetic and chemical perturbation studies, advanced imaging, computational modeling, and translational analyses to elucidate pathogen strategies and host defense mechanisms.

We particularly welcome studies that address conserved versus pathogen-specific mechanisms, biofilm biology, immune evasion, and the molecular determinants of relapse, persistence, and antimicrobial resistance. A central goal is to identify novel molecular targets that inform the development of next-generation diagnostics, therapeutics, and vaccines to reduce the global burden of pneumonia.

This Research Topic will include mechanistic, translational, and integrative studies exploring the multifaceted interactions between bacterial pathogens and host lung tissues. We invite contributions encompassing, but not limited to, the following themes:

- Host signaling pathways and innate immune responses during bacterial infection
- Complement activation, regulation, and microbial evasion strategies
- Virulence determinants and their modulation of host immune networks
- Mechanisms of bacterial adaptation, persistence, and biofilm formation
- Host–pathogen interactions in antibiotic-resistant and relapsing infections
- Spatial and single-cell profiling of infected lung microenvironments
- Cross-talk between the lung microbiome, host immunity, and invading pathogens
- Identification of novel molecular targets for diagnostic, therapeutic, and preventive interventions