Competitive Cell Death Interactions in Pulmonary Infection: Host Modulation Versus Pathogen Manipulation

Abstract

In the context of pulmonary infection, both hosts and pathogens have evolved a multitude of mechanisms to regulate the process of host cell death. The host aims to rapidly induce an inflammatory response at the site of infection, promote pathogen clearance, quickly resolve inflammation, and return to tissue homeostasis. The appropriate modulation of cell death in respiratory epithelial cells and pulmonary immune cells is central in the execution of all these processes. Cell death can be either inflammatory or anti-inflammatory depending on regulated cell death (RCD) modality triggered and the infection context. In addition, diverse bacterial pathogens have evolved many means to manipulate host cell death to increase bacterial survival and spread. The multitude of ways that hosts and bacteria engage in a molecular tug of war to modulate cell death dynamics during infection emphasizes its relevance in host responses and pathogen virulence at the host pathogen interface. This narrative review outlines several current lines of research characterizing bacterial pathogen manipulation of host cell death pathways in the lung. We postulate that understanding these interactions and the dynamics of intracellular and extracellular bacteria RCD manipulation, may lead to novel therapeutic approaches for the treatment of intractable respiratory infections.

Multinucleated Giant Cell Formation as a Portal to Chronic Bacterial Infections

“…Ku et al demonstrated that cell fusion acts as a damage-associated molecular pattern (DAMP), triggering the cGAS-STING pathway that leads to autophagic cell death [ 34 ]. The presence of bacterial effectors that manipulate cell death pathways has not been established but it is likely that they exist in some capacity, based on the successful intracellular lifestyle of Bpm and the wide array of weaponry the pathogen uses within the cell [ 43 ]. The shift from active to persister bacteria would shut down the cytoprotection and manipulation exhibited by Bpm and cause the MNGC to undergo cell death, creating foci of necrosis and inflammation, similar to those seen at the center of the mature granuloma-like lesions of chronic melioidosis patients.…”

Lobar (croupous) pneumonia: old and new data

“…PcpA (pneumococcal choline-binding protein A) may also play a certain role [ 10 ]. Recent studies also demonstrated the ability of the pathogen to induce apoptosis, necroptosis and pyroptosis [ 15 ].…”

“…Although there are numerous studies on the molecular biology of the microbiological agents causing pneumonia, defense mechanisms of the host [ 1 , 7 – 15 ] and the treatment of the disease, studies on the pathology, cause, course and epidemiology of lobar pneumonia are lacking since the middle of the 1970s. The objectives of this work were therefore to re-study the lung changes in lobar pneumonia in relation to the cause and duration of the disease in a large number of autopsies.…”

Granzyme B in Inflammatory Diseases: Apoptosis, Inflammation, Extracellular Matrix Remodeling, Epithelial-to-Mesenchymal Transition and Fibrosis

“…In cancer, anoikis resistance characterizes cancer cell anchorageindependent growth and EMT, contributing to cancer cell invasion and metastasis (62,64,65). In inflammatory diseases, as cardiovascular (66), pulmonary (67) and skin (49) diseases, and diabetes-related cardiovascular complications and retinopathy (62), aberrant anoikis is involved in excessive cell death and tissue injury.…”