5-Lipoxygenase deficiency impairs innate and adaptive immune responses during fungal infection

Area of Science:

• Immunology
• Mycology
• Biochemistry

Background:

• 5-Lipoxygenase (5-LO) products influence chronic infections.
• The specific roles of endogenous 5-LO products and exogenous leukotrienes in Histoplasma capsulatum infection require investigation.

Purpose of the Study:

• To investigate the roles of endogenous 5-lipoxygenase products and exogenous leukotrienes during Histoplasma capsulatum infection.
• To elucidate the impact of 5-LO deficiency on immune responses and fungal control in vivo and in vitro.

Main Methods:

• Utilized 5-lipoxygenase deficient (5-LO(-/-)) and wild-type (WT) mice infected with Histoplasma capsulatum.
• Assessed lung colony-forming units (CFU), nitric oxide production, and immune cell responses (neutrophils, T cells).
• Evaluated macrophage phagocytosis of IgG-opsonized H. capsulatum and the effects of exogenous leukotrienes (LTB4, LTC4).

Main Results:

• 5-LO deficiency resulted in increased lung CFU, reduced nitric oxide, and a weakened primary immune response.
• 5-LO(-/-) mice exhibited neutrophil influx and impaired effector T cell generation/recruitment.
• Macrophage phagocytosis of IgG-H. capsulatum was reduced in 5-LO deficient mice, but restored by exogenous LTB4 and LTC4.

Conclusions:

• Leukotrienes are essential for controlling chronic fungal infections, specifically histoplasmosis.
• Leukotrienes amplify both innate and adaptive immune responses, including macrophage phagocytosis and T cell recruitment.
• Targeting leukotriene pathways may offer therapeutic strategies for fungal infections.