Mononuclear phagocyte-derived interleukin-10 suppresses the innate pulmonary granuloma cytokine response in aged mice.
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.
Chiu
Bo-Chin
BC
Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Stolberg
Valerie R
VR
Freeman
Christine M
CM
Chensue
Stephen W
SW
D000375:Aging / Q000502:physiology*; D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology; D039481:CD11b Antigen / Q000276:immunology; D018925:Chemokines / Q000276:immunology; D016207:Cytokines / Q000235:genetics / Q000276:immunology*; D015769:Granuloma, Respiratory Tract / Q000276:immunology / Q000473:pathology; D006801:Humans; D007107:Immune System / Q000502:physiology; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology*; D008168:Lung / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009163:Mycobacterium bovis / Q000276:immunology; D010586:Phagocytes / Q000166:cytology / Q000276:immunology*; D015398:Signal Transduction / Q000502:physiology
D001426:Bacterial Proteins; D039481:CD11b Antigen; D018925:Chemokines; D016207:Cytokines; D016753:Interleukin-10