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CARD9 deficiencies linked to impaired neutrophil functions against Phialophora verrucosa

Pin Liang1, Xiaowen Wang, Runchao Wang

  • 1Department of Dermatology, Peking University First Hospital, Beijing, China.

Mycopathologia
|March 21, 2015
PubMed

Insights

Caspase recruitment domain-containing protein 9 (CARD9) is essential for neutrophils to kill Phialophora verrucosa. Serum opsonization offers a CARD9-independent defense mechanism against this fungal infection.

Area of Science:

  • Immunology
  • Mycology
  • Molecular Biology

Background:

  • Caspase recruitment domain-containing protein 9 (CARD9) is a key adaptor protein in C-type lectin receptor (CLR)-mediated signaling.
  • CARD9 is crucial for NF-κB activation and antifungal immunity.
  • The specific role of CARD9 in host defense against Phialophora verrucosa (P. verrucosa) is not well understood.

Purpose of the Study:

  • To investigate the function of CARD9 in polymorphonuclear neutrophils (PMNs) during P. verrucosa infection.
  • To elucidate the mechanisms of CARD9-dependent and independent host defense against P. verrucosa.

Main Methods:

  • Isolation of PMNs from CARD9-deficient patients and healthy donors.
  • Challenging isolated PMNs with P. verrucosa.
  • Assessment of P. verrucosa killing, cytokine production, reactive oxygen species (ROS) generation, and phagocytosis.

Main Results:

  • CARD9-deficient PMNs showed impaired P. verrucosa killing and reduced pro-inflammatory cytokine production compared to healthy controls.
  • Serum opsonization rescued the P. verrucosa killing defect in CARD9-deficient PMNs.
  • Reactive oxygen species generation and phagocytotic ability were normal in CARD9-deficient PMNs.

Conclusions:

  • CARD9 is indispensable for effective PMN-mediated killing of P. verrucosa.
  • Serum opsonization represents a CARD9-independent pathway for combating P. verrucosa infection.
  • Serum opsonization may hold potential as a future immunotherapy for P. verrucosa infections.

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