Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2009 Sep 15;183(6):3578-81.
doi: 10.4049/jimmunol.0901323. Epub 2009 Aug 14.

Cutting edge: Candida albicans hyphae formation triggers activation of the Nlrp3 inflammasome

Sophie Joly  1 , Ning Ma, Jeffrey J Sadler, David R Soll, Suzanne L Cassel, Fayyaz S Sutterwala
Affiliations

Cutting edge: Candida albicans hyphae formation triggers activation of the Nlrp3 inflammasome

Sophie Joly et al. J Immunol. .

Abstract

The proinflammatory cytokine IL-1beta plays an important role in antifungal immunity; however, the mechanisms by which fungal pathogens trigger IL-1beta secretion are unclear. In this study we show that infection with Candida albicans is sensed by the Nlrp3 inflammasome, resulting in the subsequent release of IL-1beta. The ability of C. albicans to switch from a unicellular yeast form into a filamentous form is essential for activation of the Nlrp3 inflammasome, as C. albicans mutants incapable of forming hyphae were defective in their ability to induce macrophage IL- 1beta secretion. Nlrp3-deficient mice also demonstrated increased susceptibility to infection with C. albicans, which is consistent with a key role for Nlrp3 in innate immune responses to the pathogen C. albicans.

PubMed Disclaimer

Conflict of interest statement

Disclosures

The authors have no financial conflict of interest.

Figures

FIGURE 1
FIGURE 1
C. albicans induces IL-1β secretion from LPS-primed Mϕ. A, BMM from WT mice were either primed with 50 ng/ml LPS or left untreated. Mϕ were infected with the C. albicans clinical isolate FC20 or ATCC strain UC820 and culture supernatants collected 6 h later; IL-1β was measured by ELISA. B, LPS-primed Mϕ were infected with C. albicans strain FC20 at the indicated MOI for 6 h; culture supernatants were collected and IL-1β release measured by ELISA. LPS-primed Mϕ were infected with the indicated C. albicans strains (C), and live, heat killed (HK) or UV killed FC20 and Zymosan (100 µg/ml) (D). IL-1β release into culture supernatants 6 h after challenge was measured by ELISA. Determinations were performed in triplicate and presented as the mean ± SEM. Results are representative of two (C, D) and three (A, B) separate experiments.
FIGURE 2
FIGURE 2
IL-1β secretion induced by C. albicans is dependent on the Nlrp3 inflammasome. A, LPS-primed BMM from WT, Nlrp3-, ASC-, caspase-1-, or Nlrc4-deficient mice were stimulated for 6 h with or without C. albicans strain FC20 at an MOI of 1:10. Culture supernatants were collected and IL-1β secretion quantified by ELISA. Determinations were performed in triplicate and expressed as the mean ± SEM. Results are representative of two separate experiments. B, Lysates from LPS- primed Mϕ from WT, Nlrp3-, ASC-, caspase-1-, or Nlrc4-deficient mice were collected after 6h exposure to C. albicans strain FC20 and immunoblotted with antibodies against the p10 subunit of caspase-1, IL-1β and GAPDH. Results are representative of two separate experiments. C, WT (n=4) and Nlrp3−/− (n=4) mice were infected i.v. with 5 × 105 CFU of C. albicans strain FC20. After 6 days C. albicans colonization was assessed in the left kidney, spleen and liver. Data are expressed as the mean ± SEM.
FIGURE 3
FIGURE 3
C. albicans bud-hyphae transition is essential for Nlrp3 inflammasome activation. A, IL-1β release from LPS-primed WT Mϕ was assessed by ELISA after 6 h exposure (MOI of 1:10) to C. albicans strain FC20 yeast and hyphae. B, LPS-primed WT Mϕ were infected with C. albicans strain SC5314 (wild-type) or the efg1Δ/Δcph1Δ/Δ̣ mutant at the indicated MOI. IL-1β release into culture supernatants 6 h after challenge was measured by ELISA. C, Lysates from LPS- primed WT Mϕ after a 6h infection with C. albicans strain SC5314 (wild-type) or the efg1Δ/Δcph1Δ/Δ̣ mutant at the indicated MOI were immunoblotted with antibodies against the p10 subunit of caspase-1 and GAPDH. D, WT mice were infected i.v. with 5 × 106 CFU of C. albicans strain SC5314 (wild-type) or the efg1Δ/Δcph1Δ/Δ̣ mutant; 4 h post infection serum IL-1β was determined by ELISA. * p = 0.0159 by two-tailed Mann Whitney test. E, LPS-primed WT Mϕ were infected with C. albicans strains FC20 and WO-1 white and opaque phenotypes at an MOI of 1:10 for 6 h and IL-1β release was measured by ELISA. F, LPS-primed WT Mϕ were infected with three strains each of C. krusei (C.k., 1: ATCC6258, 2: P31, 3: 932638), C. tropicalis (C.t., 1: T4, 2: T362, 3: T5), and C. glabrata (C.g, 1: 932273, 2: 1480, 3: 932474) and C. albicans (C.a.) FC20 at an MOI of 1:10 for 6 h and IL-1β was measured by ELISA. Determinations were performed in triplicate and presented as the mean ± SEM (A, B, E). Determinations were performed in duplicate and presented as the mean (F). Results are representative of two (B, C, E, F) and three (A) separate experiments.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Lo HJ, Köhler JR, DiDomenico B, Loebenberg D, Cacciapuoti A, Fink GR. Nonfilamentous C. albicans mutants are avirulent. Cell. 1997;90:939–949. - PubMed
    1. d'Ostiani CF, Del Sero G, Bacci A, Montagnoli C, Spreca A, Mencacci A, Ricciardi-Castagnoli P, Romani L. Dendritic cells discriminate between yeasts and hyphae of the fungus Candida albicans. Implications for initiation of T helper cell immunity in vitro and in vivo. J. Exp. Med. 2000;191:1661–1674. - PMC - PubMed
    1. Bellocchio S, Montagnoli C, Bozza S, Gaziano R, Rossi G, Mambula SS, Vecchi A, Mantovani A, Levitz SM, Romani L. The contribution of the Toll-like/IL-1 receptor superfamily to innate andadaptive immunity to fungal pathogens in vivo. J Immunol. 2004;172:3059–3069. - PubMed
    1. Vonk AG, Netea MG, van Krieken JH, Iwakura Y, van der Meer JW, Kullberg BJ. Endogenous interleukin (IL)-1α and IL-1β are crucial for host defense against disseminated candidiasis. J Infect Dis. 2006;193:1419–1426. - PubMed
    1. Pedra JH, Cassel SL SL, Sutterwala FS. Sensing pathogens and danger signals by the inflammasome. Curr Opin Immunol. 2009;21:10–16. - PMC - PubMed

Publication types

Substances

LinkOut - more resources