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Publications

Journal Article Epublish

PubMed: 40391231 DOI: 10.2147/JIR.S518653

CXCL1 and CXCL2: Key Regulators of Host Defense Against Phialophora verrucosa.

J Inflamm Res 18:6319-6329

Authors: Jiejie Lu, Qi Dong, Ruijun Zhang, Weiwei Wu, Huilan Yang

Affiliations

  • The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, People's Republic of China. Department of Dermatology, The Fifth People's Hospital of Hainan Province, Haikou, Hainan, People's Republic of China. General Hospital of Southern Theater Command, Guangzhou, Guangdong, People's Republic of China.
  • Department of Dermatology, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, Shanxi, People's Republic of China.
  • Department of Dermatology, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, Shanxi, People's Republic of China. Department of Dermatology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital, Taiyuan, Shanxi, People's Republic of China.
  • Department of Dermatology, The Fifth People's Hospital of Hainan Province, Haikou, Hainan, People's Republic of China. Department of Dermatology, Affiliated Dermatology Hospital of Hainan Medical University, Haikou, Hainan, People's Republic of China.
  • The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, People's Republic of China. General Hospital of Southern Theater Command, Guangzhou, Guangdong, People's Republic of China.

Abstract

Purpose

Dematiaceous fungi, such as Phialophora verrucosa (P. verrucosa), cause persistent infections that are difficult to treat. The purpose of this study was to investigate the roles of chemokines CXCL1 and CXCL2 in the innate immune defense against P. verrucosa infections.

Methods

A subcutaneous infection model was employed, in which live P. verrucosa conidia were administered into the footpads of wild-type C57BL/6 mice and their Cxcl1 and Cxcl2 knockout (KO) counterparts (equal numbers of male and female mice). The natural course of infection, pathological changes, and immune responses were monitored continuously over four weeks.

Results

The current results show that both CXCL1 and CXCL2 deficiencies impair fungal clearance, leading to prolonged infection as evidenced by higher fungal loads and histopathology in Cxcl1/Cxcl2 KO mice at week 4. In Cxcl1 KO mice, increased levels of inflammatory cytokines IFN-γ, G-CSF, and IL-4 were observed, likely compensating for the immunological deficiencies caused by the lack of CXCL1. Conversely, Cxcl2 KO mice exhibited impaired neutrophil infiltration early in infection, accompanied by a significant increase in macrophage infiltration.

Conclusion

These findings highlight the critical roles of CXCL1 and CXCL2 in mounting an effective immune response against dematiaceous fungi and suggest their potential as therapeutic targets.

MeSH

Immunity, Fungi, Phialophora, Infections