Episodic Aspiration with Oral Commensals Induces a MyD88-dependent, Pulmonary T-Helper Cell Type 17 Response that Mitigates Susceptibility to <i>Streptococcus pneumoniae</i>

Wu, Benjamin; Sulaiman, Imran; Tsay, J.J.; Perez, L.; Franca, Brendan; Li, Yonghua; Wang, Jing; González, Ana García; El-Ashmawy, Mariam; Carpenito, J.; Olsen, E.; Sauthoff, M.; Yie, K.; Liu, Xiuxiu; Shen, Nan; Clemente, José C.; Kapoor, Bianca; Zangari, Tonia; Mezzano, Valeria; Loomis, Cynthia A.; Weiden, Michael D.; Koralov, Sergei B.; DʼArmiento, Jeanine; Ahuja, Sunil K.; Wu, Xianwei; Weiser, Jeffrey N.; Segal, Leopoldo N.

doi:10.1164/rccm.202005-1596oc

Cited by 73 publications

(67 citation statements)

References 51 publications

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“…The discovery of Rothia as an anti-inflammatory genus in the lung microbiota raises the question whether other non-pathogenic commensals in the respiratory tract, in particular originating from the oral cavity, may have immunomodulatory properties. Recent studies in animals [73] or in vitro [74] support this hypothesis. For example, pulmonary aspiration of oral human commensals (Prevotella melaninogenica, Veillonella parvula, and Streptococcus mitis) in mice induces a T-helper cell type 17 (Th17) inflammatory phenotype that diminishes susceptibility to Streptococcus pneumoniae.…”

Section: Discussionmentioning

confidence: 91%

Rothia mucilaginosa is an anti-inflammatory bacterium in the respiratory tract of patients with chronic lung disease

et al. 2021

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Chronic airway inflammation is the main driver of pathogenesis in respiratory diseases, such as severe asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), and bronchiectasis. While the role of common pathogens in airway inflammation is widely recognized, the influence of other microbiota members is still poorly understood. Here, we show that Rothia mucilaginosa, a common resident of the oral cavity that is also often detectable in the lower airways in chronic disease, has an inhibitory effect on pathogen- and LPS-induced pro-inflammatory responses, both in vitro (3-D cell culture model) and in vivo (mouse model). Furthermore, in a cohort of adults with bronchiectasis, the abundance of Rothia spp. was negatively correlated with pro-inflammatory markers (IL-8, IL-1β) and matrix metalloproteinases (MMP-1, MMP-8 and MMP-9) in sputum. Mechanistic studies revealed that R. mucilaginosa inhibits NF-κB pathway activation by reducing the phosphorylation of IκB-α and consequently the expression of NF-κB target genes. These findings indicate that the presence of R. mucilaginosa in the lower airways potentially mitigates inflammation, which could in turn influence severity and progression of chronic respiratory disorders.

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Section: Discussionmentioning

confidence: 91%

Rothia mucilaginosa is an anti-inflammatory bacterium in the respiratory tract of patients with chronic lung disease

et al. 2021

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“…Wu et al confirmed that a single episode of aspiration of nonpathogenic bacteria ( Streptococcus mitis , Veilonella parvula , and Prevotella melaninogenica ) led to temporal changes in lower-airway dysbiosis, a prolonged increase in lung inflammatory tone, and a decrease in the susceptibility to subsequent Streptococcus pneumoniae infection [ 101 ]. They also revealed that the resulting alteration of lung inflammatory tone lasted at least 14 days and evoked sustained host immune responses including Th1 and Th17 activation, inflammasome, P38 mitogen-activated protein kinase (MAPK), and phosphoinositide 3-kinase (PI3K)/AKT signaling pathways [ 101 ]. Although it is still unclear whether the protection against secondary pneumococcal infection is pathogen specific or not, these results have provided how the most common microbial exposure in lung affects host immune responses and susceptibility to other respiratory pathogens.…”

Section: Perspectives Of Lung Microbiome Researchmentioning

confidence: 99%

The Lung Microbiome during Health and Disease

Yagi

Huffnagle

Lukacs

et al. 2021

IJMS

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Healthy human lungs have traditionally been considered to be a sterile organ. However, culture-independent molecular techniques have reported that large numbers of microbes coexist in the lung and airways. The lungs harbor diverse microbial composition that are undetected by previous approaches. Many studies have found significant differences in microbial composition between during health and respiratory disease. The lung microbiome is likely to not only influence susceptibility or causes of diseases but be affected by disease activities or responses to treatment. Although lung microbiome research has some limitations from study design to reporting, it can add further dimensionality to host-microbe interactions. Moreover, there is a possibility that extending understanding to the lung microbiome with new multiple omics approaches would be useful for developing both diagnostic and prognostic biomarkers for respiratory diseases in clinical settings.

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“…IL-17 has been show to play a central role in the clearance of pathogenic airway bacteria [ 107 ]. More recent studies indeed showed that the commensal-induced Th17 response protected mice from S. pneumoniae associated infection and mortality [ 108 ].…”

Section: Airway Apcs In Infection and Carriagementioning

confidence: 99%

“…In general, pathogenic proteobacteria induced 3–5-fold higher amounts of these cytokines than the commensal bacteria. It can be speculated that a change in the IL-23/IL-12 balance will translate into the induction of a predominant Th17-type response by the DCs as IL-23 is the key mediator of Th17 cell differentiation [ 108 , 110 ]. Further, coculture experiments with both commensals and pathogens revealed that Prevotella spp.…”

Section: Airway Apcs In Infection and Carriagementioning

confidence: 99%

Antigen-Presenting Cells in the Airways: Moderating Asymptomatic Bacterial Carriage

et al. 2021

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Bacterial respiratory tract infections (RTIs) are a major global health burden, and the role of antigen-presenting cells (APCs) in mounting an immune response to contain and clear invading pathogens is well-described. However, most encounters between a host and a bacterial pathogen do not result in symptomatic infection, but in asymptomatic carriage instead. The fact that a pathogen will cause infection in one individual, but not in another does not appear to be directly related to bacterial density, but rather depend on qualitative differences in the host response. Understanding the interactions between respiratory pathogens and airway APCs that result in asymptomatic carriage, will provide better insight into the factors that can skew this interaction towards infection. This review will discuss the currently available knowledge on airway APCs in the context of asymptomatic bacterial carriage along the entire respiratory tract. Furthermore, in order to interpret past and futures studies into this topic, we propose a standardized nomenclature of the different stages of carriage and infection, based on the pathogen’s position with regard to the epithelium and the amount of inflammation present.

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Episodic Aspiration with Oral Commensals Induces a MyD88-dependent, Pulmonary T-Helper Cell Type 17 Response that Mitigates Susceptibility to Streptococcus pneumoniae

Cited by 73 publications

References 51 publications

Rothia mucilaginosa is an anti-inflammatory bacterium in the respiratory tract of patients with chronic lung disease

Rothia mucilaginosa is an anti-inflammatory bacterium in the respiratory tract of patients with chronic lung disease

The Lung Microbiome during Health and Disease

Antigen-Presenting Cells in the Airways: Moderating Asymptomatic Bacterial Carriage

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