<i>Aspergillus fumigatus</i> effector crpA orchestrates host prostaglandin signaling to promote fungal virulence
<p dir="ltr">Conidia are the primary infection structures in <i>Aspergillus fumigatus</i>, the etiologic agent of aspergillosis. Here, we characterized CrpA (a <u>c</u>ysteine-<u>r</u>ich <u>p</u>rotein), a conidial surface-associated p...
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2025
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| Summary: | <p dir="ltr">Conidia are the primary infection structures in <i>Aspergillus fumigatus</i>, the etiologic agent of aspergillosis. Here, we characterized CrpA (a <u>c</u>ysteine-<u>r</u>ich <u>p</u>rotein), a conidial surface-associated protein important for fungal evasion and host immunity modulation. Δ<i>crpA</i> conidia elicited decreased production of pro-inflammatory cytokines and increased production of anti-inflammatory cytokine IL-10 from murine macrophages and in the lungs of infected mice. Murine macrophages exposed to Δ<i>crpA </i>conidia produce significantly higher levels of the prostaglandins PGE2 and PGD2, suggesting that deletion of CrpA modulates cytokine production through effects on eicosanoid signaling. While Δ<i>crpA </i>spores have lower virulence in larval zebrafish, this difference is abrogated in larvae that cannot produce prostaglandins. The CrpA protein can directly modulate PGE2 and cytokine production by macrophages, and solid-state NMR shows that Δ<i>crpA</i> swollen conidia present lower β-1,3-glucan and chitin than the wild-type strain, suggesting that the effects of the Δ<i>crpA</i> mutant on macrophages are due to the combinatorial effects of direct CrpA action and altered cell wall PAMP recognition. Δ<i>crpA</i> mutants are avirulent in an immunocompetent murine model of aspergillosis, and high CrpA-specific IgG responses were found in antisera from individual patients with invasive pulmonary aspergillosis, suggesting a role for CrpA in <i>A. fumigatus</i> pathogenesis<i>.</i></p><p><br></p> |
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