Differences in oxidant release by human polymorphonuclear leukocytes produced by stimulation with different phases of

J N Galgiani1

  • 1Medical and Research Services, VA Medical Center, University of Arizona College of Medicine, Tucson 85723, USA.

Insights

Mature Coccidioides immitis spherules resist human immune cells by interfering with antimicrobial oxidant production. This explains why polymorphonuclear leukocytes (PMNL) fail to inhibit mature spherule growth.

Area of Science:

  • Immunology
  • Mycology
  • Microbiology

Background:

  • Human polymorphonuclear leukocytes (PMNL) are crucial for fighting fungal infections.
  • Coccidioides immitis exhibits different growth stages with varying susceptibility to PMNL.
  • Understanding the interaction between PMNL and C. immitis stages is key to explaining fungal pathogenesis.

Purpose of the Study:

  • To investigate the differential effects of Coccidioides immitis arthroconidia, young spherules, and mature spherules on human PMNL oxidant production.
  • To elucidate the mechanisms behind the resistance of mature spherules to PMNL-mediated killing.

Main Methods:

  • PMNL were exposed to different forms of C. immitis (arthroconidia, young spherules, mature spherules) and Candida glabrata.
  • Superoxide, hydrogen peroxide, and hypochlorous acid production by PMNL were measured.
  • Catalase levels in C. immitis spherules were assessed.
  • Mature spherules were combined with arthroconidia or zymosan to observe effects on oxidant production.

Main Results:

  • PMNL inhibited arthroconidia and young spherules but not mature spherules of C. immitis.
  • Arthroconidia and young spherules stimulated hydrogen peroxide and hypochlorous acid production, while mature spherules did not.
  • Mature spherules stimulated superoxide release but interfered with hydrogen peroxide and hypochlorous acid production.
  • Low catalase levels in mature spherules did not fully explain the reduced oxidant levels.

Conclusions:

  • Mature Coccidioides immitis spherules possess mechanisms to evade PMNL-mediated oxidative killing.
  • Interference with hydrogen peroxide and hypochlorous acid production by mature spherules contributes to C. immitis resistance.
  • These findings highlight a key factor in the pathogenesis and immune evasion strategies of Coccidioides immitis.