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.
Blackstock
Rebecca
R
Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, P.O. Box 26901, Oklahoma City, OK 73190, USA. becky-blackstock@ouhsc.edu
Murphy
Juneann W
JW
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