Candida albicans Airway Exposure Primes the Lung Innate Immune Response against Pseudomonas aeruginosa Infection through Innate Lymphoid Cell Recruitment and Interleukin-22-Associated Mucosal Response

Mear, Jean Baptiste; Gosset, Philippe; Kipnis, Éric; Faure, Emmanuel; Dessein, Rodrigue; Jawhara, Samir; Fradin, Chantal; Faure, Karine; Poulain, Daniel; Sendid, Boualem; Guery, Benoît

doi:10.1128/iai.01085-13

Cited by 47 publications

(38 citation statements)

References 42 publications

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“…Recently, systemic administration of flagellins or intranasal infection with bacteria was found to activate lung type 3 innate lymphoid cells (ILC3) (25,30). These stimulated ILC3 secrete abundant amounts of interleukin 17 and interleukin 22, which are potent effectors against respiratory infections, particularly pneumococcal infections (25,42,43). Whether combination treatments activate ILC3 and play a role in the therapeutic effects remains to be studied.…”

Section: Discussionmentioning

confidence: 99%

A Toll-Like Receptor 5 Agonist Improves the Efficacy of Antibiotics in Treatment of Primary and Influenza Virus-Associated Pneumococcal Mouse Infections

Porte

Fougeron

Muñoz‐Wolf

et al. 2015

Antimicrob Agents Chemother

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g Prophylactic intranasal administration of the Toll-like receptor 5 (TLR5) agonist flagellin protects mice against respiratory pathogenic bacteria. We hypothesized that TLR5-mediated stimulation of lung immunity might improve the therapeutic index of antibiotics for the treatment of Streptococcus pneumoniae respiratory infections in mice. Intranasal administration of flagellin was combined with either oral administration of amoxicillin or intraperitoneal injection of trimethoprim-sulfamethoxazole to treat S. pneumoniae-infected animals. Compared with standalone treatments, the combination of antibiotic and flagellin resulted in a lower bacterial load in the lungs and greater protection against S. pneumoniae dissemination and was associated with an early increase in neutrophil infiltration in the airways. The antibiotic-flagellin combination treatment was, however, not associated with any exacerbation of inflammation. Moreover, combination treatment was more efficacious than standalone antibiotic treatments in the context of post-influenza virus pneumococcal infection. Lastly, TLR5 signaling was shown to be mandatory for the efficacy of the combined antibacterial therapy. This report is the first to show that combining antibiotic treatment with the stimulation of mucosal innate immunity is a potent antibacterial strategy against pneumonia.

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Section: Discussionmentioning

confidence: 99%

A Toll-Like Receptor 5 Agonist Improves the Efficacy of Antibiotics in Treatment of Primary and Influenza Virus-Associated Pneumococcal Mouse Infections

Porte

Fougeron

Muñoz‐Wolf

et al. 2015

Antimicrob Agents Chemother

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“…IL-22 also plays an important role in protection against another Gram negative Klebsiella pneumoniae in the lungs [94]. Additionally ILC-derived IL-22 is shown to be protective against both S. pneumoniae and P. aeruginosa [120, 121]. High levels of IL-22 have been reported in the pleura of patients with Tuberculosis [94, 122].…”

Section: Introductionmentioning

confidence: 99%

Biological and pathological activities of interleukin-22

et al. 2016

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Interleukin (IL)-22, a member of the IL-10 family, is a cytokine secreted by several types of immune cells including IL-22+CD4+ T cells (Th22) and IL-22 expressing innate leukocytes (ILC22). Recent studies have demonstrated that IL-22 is a key component in mucosal barrier defense, tissue repair, epithelial cell survival and proliferation. Furthermore, accumulating evidence has defined both protective and pathogenic properties of IL-22 in a number of conditions including autoimmune disease, infection and malignancy. In this Review we summarize the expression and signaling pathway and functional characteristics of the IL-22 and IL-22 receptor axis in physiological and pathological scenarios, and discuss the potential to target IL-22 signaling to treat human diseases.

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“…Although normally contained by innate and adaptive immune responses, innate immune defects and medical interventions can lead to severe mucosal candidiasis. The assault on the epithelial barrier results in an increased risk of life threatening disseminated disease as well as immunopathology, as in the case of vulvo-vaginal candidiasis, additionally C. albicans colonization has been linked with lung immune homeostasis 10,11 . Disseminated candidiasis is now the fourth most common bloodstream infection in intensive care units 12 and mortality as high as 40% makes it a major concern.…”

Section: Introductionmentioning

confidence: 99%

Modeling Mucosal Candidiasis in Larval Zebrafish by Swimbladder Injection

Gratacap

Bergeron

Wheeler

2014

JoVE

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Early defense against mucosal pathogens consists of both an epithelial barrier and innate immune cells. The immunocompetency of both, and their intercommunication, are paramount for the protection against infections. The interactions of epithelial and innate immune cells with a pathogen are best investigated in vivo, where complex behavior unfolds over time and space. However, existing models do not allow for easy spatio-temporal imaging of the battle with pathogens at the mucosal level. The model developed here creates a mucosal infection by direct injection of the fungal pathogen, Candida albicans, into the swimbladder of juvenile zebrafish. The resulting infection enables high-resolution imaging of epithelial and innate immune cell behavior throughout the development of mucosal disease. The versatility of this method allows for interrogation of the host to probe the detailed sequence of immune events leading to phagocyte recruitment and to examine the roles of particular cell types and molecular pathways in protection. In addition, the behavior of the pathogen as a function of immune attack can be imaged simultaneously by using fluorescent protein-expressing C. albicans. Increased spatial resolution of the host-pathogen interaction is also possible using the described rapid swimbladder dissection technique. The mucosal infection model described here is straightforward and highly reproducible, making it a valuable tool for the study of mucosal candidiasis. This system may also be broadly translatable to other mucosal pathogens such as mycobacterial, bacterial or viral microbes that normally infect through epithelial surfaces.

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Candida albicans Airway Exposure Primes the Lung Innate Immune Response against Pseudomonas aeruginosa Infection through Innate Lymphoid Cell Recruitment and Interleukin-22-Associated Mucosal Response

Cited by 47 publications

References 42 publications

A Toll-Like Receptor 5 Agonist Improves the Efficacy of Antibiotics in Treatment of Primary and Influenza Virus-Associated Pneumococcal Mouse Infections

A Toll-Like Receptor 5 Agonist Improves the Efficacy of Antibiotics in Treatment of Primary and Influenza Virus-Associated Pneumococcal Mouse Infections

Biological and pathological activities of interleukin-22

Modeling Mucosal Candidiasis in Larval Zebrafish by Swimbladder Injection

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