Age-related resistance of C57BL/6 mice to Cryptococcus neoformans is dependent on maturation of NKT cells.
Conflicting results have been reported regarding the ability of C57BL/6 mice to clear infections due to Cryptococcus neoformans. Examination of the various experimental protocols used suggested that C57BL/6 mice might develop the ability to resist infection as they mature. We analyzed the ability of C57BL/6 mice of different ages to respond to immunization with cryptococcal antigen or to clear a cryptococcal infection. Mice were immunized with a soluble cryptococcal culture filtrate antigen (CneF) emulsified in complete Freund's adjuvant (CneF-CFA). Delayed-type hypersensitivity (DTH) reactions elicited by the immunization were significantly stronger in 15-week-old C57BL/6 mice than in 7-week-old mice. Analysis of cryptococcal CFU 8 weeks following intratracheal infection of 7-week-old mice or 15-week-old mice revealed a relative inability of the younger animals to control the infection. Six-week-old immunized and infected mice cleared cryptococci from brain, spleen, and liver in a manner similar to that of immunized and infected 15-week-old mice. However, the older mice cleared cryptococci much more efficiently from the lungs. The possible role for NKT cells was determined by passive transfer of thymocytes from 10-week-old mice (containing mature NKT cells) or 2-week-old mice (containing immature NKT cells) to 6-week-old mice. The 10-week-old thymocytes significantly enhanced the ability of the mice to develop a DTH response after immunization with CneF-CFA, while animals treated with 2-week-old thymocytes did not improve their DTH response after immunization. The cells in the 10-week-old thymocyte population responsible for improvement of DTH responses were identified as being NK1.1 positive.
Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, P.O. Box 26901, Oklahoma City, OK 73190, USA. becky-blackstock@ouhsc.edu
Rebecca
R
Blackstock
Juneann W
JW
Murphy
D000375:Aging / Q000276:immunology*; D000818:Animals; D000946:Antigens, Fungal / Q000008:administration & dosage / Q000276:immunology; D002454:Cell Differentiation; D003453:Cryptococcosis / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control; D003455:Cryptococcus neoformans / Q000472:pathogenicity*; D005260:Female; D005620:Freund's Adjuvant / Q000008:administration & dosage / Q000276:immunology; D005657:Fungal Vaccines / Q000008:administration & dosage / Q000276:immunology; D006968:Hypersensitivity, Delayed; D007114:Immunization; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL
D000946:Antigens, Fungal; D005657:Fungal Vaccines; D005620:Freund's Adjuvant