Host responses to mucosal biofilms in the lung and gut

Abstract

The impact of the human microbiome on health and disease is of utmost importance and has been studied intensively in recent years. Microbes promote immune system development and are essential to the production and absorption of nutrients for the host but are also implicated in disease pathogenesis. Particularly, bacterial biofilms have long been recognized as contributors to chronic infections and diseases in humans. However, our understanding of how the host responds to the presence of biofilms, specifically the immune response to biofilms, and how this contributes to disease pathogenesis is limited. This review aims to highlight what is known about biofilm formation and in vivo models available for the biofilm study. We critique the contribution of biofilms to human diseases, focusing on the lung diseases, cystic fibrosis and chronic obstructive pulmonary disease, and the gut diseases, inflammatory bowel disease and colorectal cancer.

Understanding Pseudomonas aeruginosa–Host Interactions: The Ongoing Quest for an Efficacious Vaccine

“…A recent review outlined several studies showing that CF patients chronically colonised with P. aeruginosa had greater levels of IL-3, IL-4, and secreted immunoglobulin A (Th2 markers) and lower IFN-γ secretion, compared with intermittently colonised patients or those without P. aeruginosa [89]. Hence, the enhancement of the Th1 response may reduce inflammation in the lung by decreasing recruitment of neutrophils due to the reduction in the neutrophil chemoattractant IL-8.…”

“…A marked increase in anti-PcrV IgG1 titres but a decrease in IgG2a titres was observed, indicating a Th2-biased immune response and highlighting a key limitation of alum, it induces strong Th2-mediated immune responses, as a poor inducer of cellular immune responses [93]. As mentioned in Section 3.3, the adaptive response to P. aeruginosa infections is characterised by a skewed Th2 response [86], with high levels of Th2 markers (IL-3, IL-4) and low levels of Th1 markers (IFN-γ), as observed in patients with chronic P. aeruginosa infections [89]. Thus, adjuvants such as alum that increase the Th2 response may not be optimal for increased protection against P. aeruginosa, and may even be detrimental.…”

“…The ability of dmLT to support antibody responses in addition to Th1/Th17 cellular immunity is significant and offers a clear advantage, particularly for those pathogens that require both humoral and cellular responses for protection [95]. Notwithstanding these data, these studies mostly used acute infection models, so the question remains as to whether a Th17 response would be beneficial in chronic infections or if, on the contrary, as stated by other authors [89,92], potentially harmful in these stages of P. aeruginosa infections.…”

Influence of Hypoxia on the Epithelial-Pathogen Interactions in the Lung: Implications for Respiratory Disease

“…The formation of multicellular microbial communities called biofilms is a critical step for pathogens during colonization of the lung, enabling survival and persistence in the challenging environment by attaching to a living surface ( 142 , 143 ). Many different microbes reside in biofilms and the majority of persistent infections involve biofilms ( 144 ).…”

Co‐ and polymicrobial infections in the gut mucosa: The host–microbiota–pathogen perspective

“…The best characterized models of polymicrobial interaction are associated with the oral cavity and respiratory mucosa (Domingue, Drewes, Merlo, Housseau, & Sears, 2020; Lamont, Koo, & Hajishengallis, 2018; Peters, Jabra‐Rizk, O'May, Costerton, & Shirtliff, 2012; Welp & Bomberger, 2020). Here, however, we will discuss the concept of co‐ and polymicrobial infections in the context of the intestinal mucosa, with specific focus on the interplay between the host, the gastrointestinal microbiota and the pathogenic organisms.…”