1. Mononuclear Phagocyte-Derived Interleukin-10 Suppresses the Innate Pulmonary Granuloma Cytokine Response in Aged Mice
- Author
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Stephen W. Chensue, Valerie R. Stolberg, Bo Chin Chiu, and Christine M. Freeman
- Subjects
Male ,Chemokine ,Aging ,Phagocyte ,Granuloma, Respiratory Tract ,Pathology and Forensic Medicine ,Mice ,Immune system ,Bacterial Proteins ,medicine ,Animals ,Humans ,Lung ,Phagocytes ,CD11b Antigen ,biology ,Interleukin ,Mononuclear phagocyte system ,Acquired immune system ,Mycobacterium bovis ,Interleukin-10 ,Mice, Inbred C57BL ,Interleukin 10 ,medicine.anatomical_structure ,Immune System ,Immunology ,biology.protein ,Leukocytes, Mononuclear ,Cytokines ,Tumor necrosis factor alpha ,Chemokines ,Regular Articles ,Signal Transduction - Abstract
Granulomas are sequestration responses observed in a wide variety of clinical conditions, including mycobacterial infection. We previously reported impaired adaptive, Th1 cell-mediated pulmonary granuloma formation in response to bead-immobilized Mycobacterium bovis-purified protein derivative in aged mice. To reveal determinants of age-related immune deficits, the present study examined the effect of aging on early innate stage pulmonary granuloma formation. Aged mice formed more neutrophil-rich innate granulomas with augmented CXCL2 expression followed by a pattern of rapid decay of tumor necrosis factor-alpha, interleukin (IL)-6, CCL3, and CXCL2. This was associated with enhanced IL-10 expression. Blockade of IL-10 signaling with anti-IL-10 receptor antibody reversed the age-related decay. Intracellular flow cytometric analysis revealed that CD11b(+)Gr-1(+/-) mononuclear phagocytes were the primary leukocyte sources of IL-10 in lungs, and their numbers were increased in aged mice. When exposed to purified protein derivative in vitro, young and old CD11b(+)Gr-1(+/-) mononuclear phagocytes from blood or lung had comparable IL-10 expression, suggesting in vivo signals in the aged environment enhanced the number of IL-10-producing cells in the aged lung. Our findings reveal a novel mechanism of age-associated IL-10 mediated pulmonary immune suppression with the potential to alter downstream adaptive immunity.
- Published
- 2007