Commensal Bacteroidetes protect against Klebsiella pneumoniae colonization and transmission through IL-36 signalling

Abstract

The microbiota primes immune defences but the identity of specific commensal microbes which protect against infection is unclear. Conversely, how pathogens compete with the microbiota to establish their host niche is also poorly understood. Here, we investigate the antagonism between the microbiota and Klebsiella pneumoniae during colonization and transmission. We discover that maturation of the microbiota drives the development of distinct immune defence programs in the upper airway and intestine to limit K. pneumoniae colonization within these niches. Immune protection in the intestine depends on the development of Bacteroidetes, IL-36 signalling and macrophages. This effect of Bacteroidetes requires their conserved commensal colonization factor (CCF) polysaccharide utilization locus. Conversely, in the upper airway, Proteobacteria prime immunity through IL-17A, but K. pneumoniae overcomes these defences through encapsulation to effectively colonize this site. Ultimately, we find that host-to-host spread of K. pneumoniae occurs principally from its intestinal reservoir, and that CCF-producing Bacteroidetes are sufficient to prevent transmission between hosts through IL-36. Thus, our study provides mechanistic insight into when, where and how commensal Bacteroidetes protect against K. pneumoniae colonization and contagion, providing insight into how these protective microbes could be harnessed to confer population-level protection against K. pneumoniae infection.

An Animal Model to StudyKlebsiella pneumoniaeGastro-Intestinal Colonization and Host-to-Host Transmission

“…Klebsiella pneumoniae disease manifestations in the respiratory and urinary tract have been extensively modeled in animals (4). However, the gastrointestinal mucosal surface, also colonized readily by Kpn has not been the focus of many scientific studies (51, 52). In this report, we describe a murine model of oral infection of K. pneumoniae to study GI colonization and host-to-host transmission.…”

Clinical observation and prognostic analysis of patients with Klebsiella pneumoniae bloodstream infection

“…At the same time, we observed that the APACHE II score (p < 0.001) and SOFA score (p < 0.001) were higher in the death group. In the death group, the hospitalization days before BSI were relatively longer (8 [4,18] days versus 14 [5,22] days, p = 0.015).…”

“…These facultative anaerobic bacteria have low nutritional requirements, no flagella, no spores, an obvious capsule, and strong resistance to the outside world. Klebsiella pneumoniae can colonize in the respiratory tract and skin, as well as become aerosolized (3)(4)(5). There are a variety of clinical manifestations, including bloodstream infection (BSI), pulmonary infection, urinary tract infection, abdominal infection, and so forth (6,7).…”

IL‐36 cytokines and gut immunity

“…the LCN2 and reg3 family), IEC proliferation and mucins suggests that it may have direct/indirect effects on the composition of the microbiota. 10,14,16,76 IL-36R signalling has also been shown to alter the microbiota composition and protect mice from obesity. 10 The altered microbiota in genetically modified mice lacking IL-36R could potentially influence defective recovery following DSS-mediated acute intestinal inflammation.…”