Arming Th17 Cells for Antifungal Host Defense

Gladiator, André; Trautwein-Weidner, Kerstin; Bär, Eva; LeibundGut‐Landmann, Salomé

doi:10.1007/s12281-013-0130-5

Cited by 3 publications

(1 citation statement)

References 67 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our results demonstrate that cell wall changes following neutrophil attack do increase recognition of β-glucan and also specifically elicit more IL-6, but not TNF-α, from macrophages when compared to controls. Elevated IL-6 production, in particular, may be important as it participates in the induction of Th17 responses which are important for antifungal immunity [ 49 – 51 ]. Interestingly, some of the increased macrophage response was not blocked by neutralizing anti-Dectin-1 antibodies, suggesting that either other cell wall changes beyond β-glucan unmasking may play a role or the antibody is less effective in our system.…”

Section: Discussionmentioning

confidence: 99%

Neutrophil Attack Triggers Extracellular Trap-Dependent Candida Cell Wall Remodeling and Altered Immune Recognition

et al. 2016

View full text Add to dashboard Cite

Pathogens hide immunogenic epitopes from the host to evade immunity, persist and cause infection. The opportunistic human fungal pathogen Candida albicans, which can cause fatal disease in immunocompromised patient populations, offers a good example as it masks the inflammatory epitope β-glucan in its cell wall from host recognition. It has been demonstrated previously that β-glucan becomes exposed during infection in vivo but the mechanism behind this exposure was unknown. Here, we show that this unmasking involves neutrophil extracellular trap (NET) mediated attack, which triggers changes in fungal cell wall architecture that enhance immune recognition by the Dectin-1 β-glucan receptor in vitro. Furthermore, using a mouse model of disseminated candidiasis, we demonstrate the requirement for neutrophils in triggering these fungal cell wall changes in vivo. Importantly, we found that fungal epitope unmasking requires an active fungal response in addition to the stimulus provided by neutrophil attack. NET-mediated damage initiates fungal MAP kinase-driven responses, particularly by Hog1, that dynamically relocalize cell wall remodeling machinery including Chs3, Phr1 and Sur7. Neutrophil-initiated cell wall disruptions augment some macrophage cytokine responses to attacked fungi. This work provides insight into host-pathogen interactions during disseminated candidiasis, including valuable information about how the C. albicans cell wall responds to the biotic stress of immune attack. Our results highlight the important but underappreciated concept that pattern recognition during infection is dynamic and depends on the host-pathogen dialog.

show abstract

Section: Discussionmentioning

confidence: 99%