IL-17A attracts inflammatory cells in murine lung infection with P. aeruginosa

Wonnenberg, Bodo; Jungnickel, Christopher; Honecker, Anja; Wolf, Lisa; Voss, Meike; Bischoff, Markus; Tschernig, Thomas; Herr, Christian; Bals, Robert; Beißwenger, Christoph

doi:10.1177/1753425916668244

Cited by 31 publications

(22 citation statements)

References 37 publications

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“…Although the beneficial vs. detrimental role of IL-17 signaling (e.g. in IL-17 −/− or IL-17R −/− mice) in acute P. aeruginosa infection is still debated [57,58], the absence of IL-17 signaling has been linked to increased incidence of chronic P. aeruginosa infection, increased bacterial burden and decreased survival in recent studies [59,60]. Lore, et al noted, however, that chronically infected IL-17a −/− mice showed less pulmonary inflammation and tissue damage than wild-type counterparts, consistent with IL-17-mediated increases in matrix metalloproteinase secretion and tissue remodeling [61].…”

Section: Immune Recognition and Response To P Aeruginosa Infectionmentioning

confidence: 99%

Inflammation: A Double-Edged Sword in the Response to Pseudomonas aeruginosa Infection

Lin

Kazmierczak²

2017

J Innate Immun

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The Gram-negative opportunistic pathogen Pseudomonas aeruginosa exploits failures of barrier defense and innate immunity to cause acute infections at a range of anatomic sites. We review the defense mechanisms that normally protect against P. aeruginosa pulmonary infection, as well as the bacterial products and activities that trigger their activation. Innate immune recognition of P. aeruginosa is critical for pathogen clearance; nonetheless, inflammation is also associated with pathogen persistence and poor host outcomes. We describe P. aeruginosa adaptations that improve this pathogen's fitness in the inflamed airway, and briefly discuss strategies to manipulate inflammation to benefit the host. Such adjunct therapies may become increasingly important in the treatment of acute and chronic infections caused by this multi-drug-resistant pathogen.

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Section: Immune Recognition and Response To P Aeruginosa Infectionmentioning

confidence: 99%

Inflammation: A Double-Edged Sword in the Response to Pseudomonas aeruginosa Infection

Lin

Kazmierczak²

2017

J Innate Immun

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“…TH17 cells can release a large amount of IL‐17A to promote G‐CSF and KC secretion, and G‐CSF can mobilize neutrophils from the bone marrow to peripheral blood . KC can induce the chemotaxis of pro‐inflammatory cells in particular neutrophils to the lung, consequently increasing inflammatory monocytes and neutrophils and lymphocytes in the BALF of the mice with AE‐IPF and exacerbating the local inflammatory responses in the lung. Compared with the WT mice, the IL‐17A ‐/‐ mice showed reduced G‐CSF and KC concentrations in the BALF, fewer inflammatory monocytes and neutrophils in the BALF, attenuated lung inflammation and dysfunction and higher survival rate.…”

Section: Discussionmentioning

confidence: 99%

IL‐17A contributes to HSV1 infection‐induced acute lung injury in a mouse model of pulmonary fibrosis

Chen

Qiu

Zhao

et al. 2018

J Cellular Molecular Medi

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BackgroundPatients with idiopathic pulmonary fibrosis (IPF) often experience acute exacerbation (AE) after an episode of common cold.AimsTo establish a mouse model of virus infection‐induced AE‐IPF and investigate the mechanism underlying the AE‐IPF.MethodsHerpes simplex virus 1 (HSV1) was inoculated intranasally to wild‐type (WT) and IL‐17A gene knockout (IL‐17A‐/‐) mice 21 days after intratracheal administration of bleomycin (BLM).Results HSV1 infection caused acute exacerbation in mice with BLM‐induced fibrosis. Compared with the BLM+Saline mice, the mice with BLM+HSV1 showed significantly higher acute lung injury (ALI) score (P < 0.0001), lower survival rate (100% vs 21.4%, P < 0.0001), poorer lung function and higher inflammatory response representing by increased total inflammatory cells in bronchoalveolar lavage fluid (BALF) (P = 0.0323), increased proportion of Th17 cells in peripheral blood (P = 0.0004) and higher inflammatory factors in BALF. In addition, HSV1 infection increased the expression of endoplasmic reticulum stress (ERS)‐related proteins in mice with BLM‐induced fibrosis. The inhibition of ERS by tauroursodeoxycholic acid (TUDCA, an ERS inhibitor) significantly reduced the IL‐17A levels in BALF (P = 0.0140) and TH17 cells in the peripheral blood (P = 0.0084) of mice with BLM+HSV1, suggesting that suppression of ERS may reduce TH17 response in mice with AE‐IPF. Compared with WT mice with BLM+HSV1, IL‐17A‐/‐ mice with BLM+HSV1 had lower ALI score (P = 0.0119), higher survival rate (78.6% vs 21.4%, P = 0.004), improved lung function, and milder inflammatory response.Conclusions HSV1 infection in addition to BLM‐induced IPF can successfully establish AE‐IPF in mice. IL‐17A and ERS promote lung inflammation in AE‐IPF development.

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“…Interestingly, however, IL-17A is nearly undetectable in naïve infants, and vaccination increases IL-17A levels (14). Mice deficient in IL-17A and IL-17RA demonstrate increased susceptibility to a large number of bacterial pathogens that cause lung diseases (15, 16). Even so, the mechanism of IL-17A production during S. pneumoniae infection is largely unknown.…”

Section: Introductionmentioning

confidence: 99%

ATF3 Stimulates IL-17A by Regulating Intracellular Ca2+/ROS-Dependent IL-1β Activation During Streptococcus pneumoniae Infection

Lee

Kim

et al. 2018

Front. Immunol.

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Activating transcription factor-3 (ATF3) in the ER stress pathway induces cytokine production and promotes survival during gram-positive bacterial infection. IL-17A is a critical cytokine that is essential for clearance of Streptococcus pneumoniae. However, the mechanism by which ATF3 induces IL-17A production remains unknown. Here, we show that ATF3 induces IL-17A production via NLRP3 inflammasome-dependent IL-1β secretion. Survival rates were comparable in IL-17A-depleted and ATF3 KO mice but were lower than in WT mice treated with isotype control, indicating that ATF3 positively regulated IL-17A production. Indeed, ATF3 KO mice showed a marked reduction in IL-17A protein and mRNA expression compared to levels in WT mice. Moreover, mitochondrial IL-1β production by bone marrow-derived macrophages was significantly reduced in ATF3 KO mice as a result of the disruption of cellular ROS and Ca2+ homeostasis. Accordingly, ATF3 KO mice displayed diminished survival and bacterial clearance following S. pneumoniae infection. Taken together, these data suggest a mechanism in which macrophage ATF3 promotes IL-17A production in γδ T cells to rapidly induce host defenses during early S. pneumoniae infection.

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IL-17A attracts inflammatory cells in murine lung infection with P. aeruginosa

Cited by 31 publications

References 37 publications

Inflammation: A Double-Edged Sword in the Response to <b><i>Pseudomonas aeruginosa</i></b> Infection

Inflammation: A Double-Edged Sword in the Response to <b><i>Pseudomonas aeruginosa</i></b> Infection

IL‐17A contributes to HSV1 infection‐induced acute lung injury in a mouse model of pulmonary fibrosis

ATF3 Stimulates IL-17A by Regulating Intracellular Ca2+/ROS-Dependent IL-1β Activation During Streptococcus pneumoniae Infection

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