IL-5 Is Required for Eosinophil Recruitment, Crystal Deposition, and Mononuclear Cell Recruitment During a Pulmonary Cryptococcus neoformans Infection in Genetically Susceptible Mice (C57BL/6)

• Published in: The Journal of immunology (1950) 1998-03, Vol.160 (5), p.2393-2400
• Main Authors: Huffnagle, Gary B, Boyd, Michael B, Street, Nancy E, Lipscomb, Mary F
• Format: Article
• Language: English
• Subjects: AIDS/HIV; Animals; CD4-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - immunology; Cell Movement - immunology; Chronic Disease; Cryptococcosis - genetics; Cryptococcosis - immunology; Cryptococcosis - microbiology; Cryptococcosis - pathology; Crystallization; Disease Susceptibility; Eosinophilia - genetics; Eosinophilia - immunology; Eosinophilia - microbiology; Eosinophilia - pathology; Eosinophils - immunology; Eosinophils - pathology; Female; Glycoproteins - metabolism; Interleukin-5 - physiology; Leukocytes, Mononuclear - immunology; Leukocytes, Mononuclear - pathology; Lung - immunology; Lung - microbiology; Lung - pathology; Lung Diseases, Fungal - genetics; Lung Diseases, Fungal - immunology; Lung Diseases, Fungal - microbiology; Lung Diseases, Fungal - pathology; Lysophospholipase; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred CBA
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.160.5.2393

CBA/J (highly resistant), BALB/c (moderately resistant), and C57BL/6 (susceptible) mice displayed three resistance patterns following intratracheal inoculation of Cryptococcus neoformans 52. The inability to clear the infection correlated with the duration of the eosinophil infiltrate in the lungs. The role of IL-5 in promoting the pulmonary eosinophilia and subsequent inflammatory damage in susceptible C57BL/6 mice was investigated. C57BL/6 mice developed a chronic alveolar, peribronchiolar, and perivascular eosinophilia following C. neoformans infection. This resulted in the accumulation of intracellular Charcot-Leyden-like crystals in alveolar macrophages by wk 4 and the extracellular deposition of these crystals in the bronchioles with associated destruction of airway epithelium by wk 6. IL-5 mRNA was expressed in the lungs, and injections of anti-IL-5 mAb prevented eosinophil recruitment and crystal deposition but did not alter cryptococcal clearance. Depletion of CD4+ T cells (but not CD8+) ablated IL-5 production by lung leukocytes in vitro and eosinophil recruitment in vivo. Neutralization of IL-5 also inhibited the recruitment of macrophages, CD8+ T lymphocytes, and B lymphocytes by 47 to 57%. Anti-IL-5 mAb inhibited CD4+ T lymphocyte recruitment by 30% but did not affect neutrophil recruitment. Thus, the development of a chronic eosinophil infiltrate in the lungs of C. neoformans-infected C57BL/6 mice is a nonprotective immune response that causes significant lung pathology. Furthermore, IL-5 promotes the recruitment and activation of eosinophils, resulting in the recruitment of additional macrophages and lymphocytes into the lungs.