白色念珠菌,最常见的条件病原真菌之一,会导致局部表面感染和致命的全身感染,尤其是在免疫功能低下的人群中。分泌型免疫球蛋白A(sIgA)是调节白色念珠菌致病性的重要免疫蛋白。然而,sIgA对白色念珠菌的直接作用和机制尚不清楚。这里,我们研究了sIgA对白色念珠菌菌丝生长和口腔上皮细胞的毒力。我们的结果表明,sIgA显著抑制白色念珠菌菌丝生长,附着力,与IgG相比,对口腔上皮细胞的损害。根据转录组和RT-PCR分析,sIgA显著影响麦角甾醇生物合成途径。此外,sIgA显著降低麦角固醇水平,而添加外源麦角甾醇恢复白色念珠菌菌丝生长和粘附口腔上皮细胞,表明sIgA通过降低其麦角固醇水平抑制菌丝的生长和白色念珠菌的致病性。通过采用关键基因突变体(erg11Δ/Δ,3Δ/Δ,和erg3Δ/Δerg11Δ/Δ)来自麦角甾醇途径,sIgA失去了对这些突变体的菌丝抑制,而sIgA也降低了erg11Δ/Δ和erg3Δ/Δ的抑制作用,并失去了erg3Δ/Δerg11Δ/Δ对口腔上皮细胞粘附的抑制作用,进一步证明了通过麦角固醇途径对sIgA的菌丝抑制。我们首次证明sIgA通过影响麦角甾醇生物合成抑制白色念珠菌菌丝发育和毒力,并表明麦角甾醇是白色念珠菌-宿主细胞相互作用的关键调节因子。关键点:•sIgA抑制白色念珠菌菌丝生长•sIgA抑制白色念珠菌对宿主细胞的毒力•sIgA通过降低其麦角固醇水平影响白色念珠菌菌丝和毒力。
Candida albicans, one of the most prevalent conditional pathogenic fungi, can cause local superficial infections and lethal systemic infections, especially in the immunocompromised population. Secretory immunoglobulin A (sIgA) is an important immune protein regulating the pathogenicity of C. albicans. However, the actions and mechanisms that sIgA exerts directly against C. albicans are still unclear. Here, we investigated that sIgA directs against C. albicans hyphal growth and virulence to oral epithelial cells. Our results indicated that sIgA significantly inhibited C. albicans hyphal growth, adhesion, and damage to oral epithelial cells compared with IgG. According to the transcriptome and RT-PCR analysis, sIgA significantly affected the ergosterol biosynthesis pathway. Furthermore, sIgA significantly reduced the ergosterol levels, while the addition of exogenous ergosterol restored C. albicans hyphal growth and adhesion to oral epithelial cells, indicating that sIgA suppressed the growth of hyphae and the pathogenicity of C. albicans by reducing its ergosterol levels. By employing the key genes mutants (erg11Δ/Δ, erg3Δ/Δ, and erg3Δ/Δ erg11Δ/Δ) from the ergosterol pathway, sIgA lost the hyphal inhibition on these mutants, while sIgA also reduced the inhibitory effects of erg11Δ/Δ and erg3Δ/Δ and lost the inhibition of erg3Δ/Δ erg11Δ/Δ on the adhesion to oral epithelial cells, further proving the hyphal repression of sIgA through the ergosterol pathway. We demonstrated for the first time that sIgA inhibited C. albicans hyphal development and virulence by affecting ergosterol biosynthesis and suggest that ergosterol is a crucial regulator of C. albicans-host cell interactions. KEY POINTS: • sIgA repressed C. albicans hyphal growth • sIgA inhibited C. albicans virulence to host cells • sIgA affected C. albicans hyphae and virulence by reducing its ergosterol levels.