IL-10 Controls Aspergillus fumigatus- and Pseudomonas aeruginosa-Specific T-Cell Response in Cystic Fibrosis

Casaulta, Carmen; Schöni, Martin H.; Weichel, Michael; Crameri, Reto; Jutel, Marek; Daigle, Isabelle; Akdiş, Mübeccel; Blaser, Kurt; Akdiş, Cezmi A.

doi:10.1203/01.pdr.0000047528.79014.cf

Cited by 15 publications

(7 citation statements)

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“…PBMC from CF patients secreted increased amounts of IL-10 compared to healthy controls when exposed to recombinant A. fumigatus antigens (14). Blockade of IL-10 resulted in enhanced type 1 responses, suggesting a role for IL-10 in inhibiting A. fumigatus T cell responses in CF (14). This could represent an adaptive mechanism in CF patients in response to a prolonged cycle of lung inflammation and damage due to chronic infection with A. fumigatus and other organisms.…”

Section: Discussionmentioning

confidence: 99%

“…Even with antimicrobial treatment and eventual clearance of NTM, it is conceivable that CF patients coinfected with A. fumigatus and M. abscessus could experience a decline in lung function due to prolonged lung damage during a year-long treatment course. PBMC from CF patients secreted increased amounts of IL-10 compared to healthy controls when exposed to recombinant A. fumigatus antigens (14). Blockade of IL-10 resulted in enhanced type 1 responses, suggesting a role for IL-10 in inhibiting A. fumigatus T cell responses in CF (14).…”

Section: Discussionmentioning

confidence: 99%

“…Previous work has demonstrated that peripheral blood mononuclear cells (PBMC) from CF patients, in comparison to PBMC from healthy controls, secreted increased IL-10 levels when exposed to A. fumigatus antigens (13). Upon blockade of IL-10, type 1 responses were enhanced, suggesting that IL-10 may play a role in inhibiting A. fumigatus T cell responses in CF (14). This raises the question of whether such inhibition of the immune response by A. fumigatus may affect concomitant immunity to NTM infections and their associated pathology.…”

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confidence: 99%

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Aspergillus fumigatus Preexposure Worsens Pathology and Improves Control of Mycobacterium abscessus Pulmonary Infection in Mice

et al. 2018

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Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. Mutations in this chloride channel lead to mucus accumulation, subsequent recurrent pulmonary infections, and inflammation, which, in turn, cause chronic lung disease and respiratory failure. Recently, rates of nontuberculous mycobacterial (NTM) infections in CF patients have been increasing. Of particular relevance is infection with , which causes a serious, life-threatening disease and constitutes one of the most antibiotic-resistant NTM species. Interestingly, an increased prevalence of NTM infections is associated with worsening lung function in CF patients who are also coinfected with We established a new mouse model to investigate the relationship between and pulmonary infections. In this model, animals exposed to and coinfected with exhibited increased lung inflammation and decreased mycobacterial burden compared with those of mice infected with alone. This increased control of infection in coinfected mice was mucus independent but dependent on both transcription factors T-box 21 (Tbx21) and retinoic acid receptor (RAR)-related orphan receptor gamma t (RORγ-t), master regulators of type 1 and type 17 immune responses, respectively. These results implicate a role for both type 1 and type 17 responses in control in-coinfected lungs. Our results demonstrate that , an organism found commonly in CF patients with NTM infection, can worsen pulmonary inflammation and impact control in a mouse model.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Aspergillus fumigatus Preexposure Worsens Pathology and Improves Control of Mycobacterium abscessus Pulmonary Infection in Mice

et al. 2018

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“…Most ex vivo studies have been done with one live microorganism and antigens of the partner, or killed microorganisms. For examples, in one ex vivo model of M. abscessus infecting macrophages, fungal products were added prior the bacterial infection and activation of macrophages was investigated [15], and in the other ex vivo model, killed P. aeruginosa and A. fumigatus antigens were used to stimulate CF peripheral blood mononuclear cells (PBMC), and cytokines were quantified [82]. Only one in vitro immune cell model of co-infection with different strains of alive P. aeruginosa and A. fumigatus in CF bronchial epithelial cell lines (CFBE cells derived from a cystic fibrosis patient homozygous for the ΔF508 CFTR mutation) has been reported [77].…”

Section: How Are Mixed Bacterial–fungal Infections Seen By the Hosmentioning

confidence: 99%

“…The lack of enhancement of pro-inflammatory responses for the majority of tested co-infections with other P. aeruginosa and A. fumigatus clinical strains suggests that their association may not generally further exacerbate the inflammatory response, compared to mono-cell infection [77]. In the ex vivo model of A. fumigatus and P. aeruginosa stimulating PBMC, secretion of increased amount of the anti-inflammatory IL10, inhibiting A. fumigatus T cell responses, was observed, suggesting an adaptive mechanism observed in CF patients in response to prolonged cycles of lung inflammation and damages due to infections [82]. Using the ex vivo model of co-infected by M. abscessus and fungal antigens, the authors demonstrated that β1,3 glucans treatment of macrophages improved M. abscessus control [15].…”

Section: How Are Mixed Bacterial–fungal Infections Seen By the Hosmentioning

confidence: 99%

Interactions between Aspergillus fumigatus and Pulmonary Bacteria: Current State of the Field, New Data, and Future Perspective

Briard

Mislin

Latgé

et al. 2019

JoF

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Aspergillus fumigatus and Pseudomonas aeruginosa are central fungal and bacterial members of the pulmonary microbiota. The interactions between A. fumigatus and P. aeruginosa have only just begun to be explored. A balance between inhibitory and stimulatory effects on fungal growth was observed in mixed A. fumigatus–P. aeruginosa cultures. Negative interactions have been seen for homoserine-lactones, pyoverdine and pyochelin resulting from iron starvation and intracellular inhibitory reactive oxidant production. In contrast, several types of positive interactions were recognized. Dirhamnolipids resulted in the production of a thick fungal cell wall, allowing the fungus to resist stress. Phenazines and pyochelin favor iron uptake for the fungus. A. fumigatus is able to use bacterial volatiles to promote its growth. The immune response is also differentially regulated by co-infections.

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Is cystic fibrosis a TH17 disease?

2007

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Cystic Fibrosis (CF) is the most common lethal genetic disease in the Caucasian population and typically results in the development of bronchial inflammation, bronchiectasis, the progressive loss of lung function and ultimately death. Recently it has been shown that products of the Th(17) subset of T-cells, specifically, IL-17A and IL-17F are elevated in the sputum of CF patients. This review will go over experimental evidence supporting a role for the IL- 23/IL-17 axis in CF lung inflammation.

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IL-10 Controls Aspergillus fumigatus- and Pseudomonas aeruginosa-Specific T-Cell Response in Cystic Fibrosis

Cited by 15 publications

References 46 publications

Aspergillus fumigatus Preexposure Worsens Pathology and Improves Control of Mycobacterium abscessus Pulmonary Infection in Mice

Aspergillus fumigatus Preexposure Worsens Pathology and Improves Control of Mycobacterium abscessus Pulmonary Infection in Mice

Interactions between Aspergillus fumigatus and Pulmonary Bacteria: Current State of the Field, New Data, and Future Perspective

Is cystic fibrosis a TH17 disease?

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