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PTP1B deficiency in myeloid cells increases susceptibility to Candida albicans systemic infection by modulating antifungal immunity

Summary

This research shows that a protein called PTP1B plays an important role in protecting the body against dangerous fungal infections caused by Candida albicans. When mice lacked this protein in their immune cells, they were much more susceptible to the infection and showed severe illness. The study found that PTP1B helps immune cells like macrophages and neutrophils fight the fungus effectively, and blocking this protein could actually make fungal infections worse.

Background

Invasive candidiasis caused by Candida albicans poses a significant threat to immunocompromised patients with high mortality rates. Protein tyrosine phosphatase 1B (PTP1B) is a regulator of immunoreceptor signaling and inflammatory responses. Understanding PTP1B’s role in fungal immunity could inform new therapeutic strategies.

Objective

To determine the critical role of myeloid cell-intrinsic PTP1B in antifungal immunity against systemic Candida albicans infection. The study examined how PTP1B deficiency in myeloid cells affects susceptibility to fungal infection and the mechanisms controlling antifungal immune responses.

Results

LysM PTP1B−/− mice showed increased susceptibility with reduced survival, greater weight loss, and elevated fungal burdens in organs. These mice exhibited heightened proinflammatory responses, impaired neutrophil maturation and reduced ROS production, and decreased macrophage phagocytosis and killing capacity. Proteomic analysis revealed enrichment of type I interferon-regulated proteins in PTP1B-deficient macrophages.

Conclusion

PTP1B functions as a critical negative regulator of antifungal immunity, balancing antifungal activity with systemic toxicity and inflammation. Targeting specific PTP1B-dependent pathways may offer new strategies for enhancing host defense against C. albicans while minimizing fungal-induced immunopathology.
  • Published in:mBio,
  • Study Type:Experimental Animal Study,
  • Source: PMID: 40879376
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