Impact of surfactant protein D, interleukin-5, and eosinophilia on Cryptococcosis.
Cryptococcus neoformans is an opportunistic fungal pathogen that initiates infection following inhalation. As a result, the pulmonary immune response provides a first line of defense against C. neoformans. Surfactant protein D (SP-D) is an important regulator of pulmonary immune responses and is typically host protective against bacterial and viral respiratory infections. However, SP-D is not protective against C. neoformans. This is evidenced by previous work from our laboratory demonstrating that SP-D-deficient mice infected with C. neoformans have a lower fungal burden and live longer than wild-type (WT) control animals. We hypothesized that SP-D alters susceptibility to C. neoformans by dysregulating the innate pulmonary immune response following infection. Thus, inflammatory cells and cytokines were compared in the bronchoalveolar lavage fluid from WT and SP-D(-/-) mice after C. neoformans infection. Postinfection, mice lacking SP-D have reduced eosinophil infiltration and interleukin-5 (IL-5) in lung lavage fluid. To further explore the interplay of SP-D, eosinophils, and IL-5, mice expressing altered levels of eosinophils and/or IL-5 were infected with C. neoformans to assess the role of these innate immune mediators. IL-5-overexpressing mice have increased pulmonary eosinophilia and are more susceptible to C. neoformans infection than WT mice. Furthermore, susceptibility of SP-D(-/-) mice to C. neoformans infection could be restored to the level of WT mice by increasing IL-5 and eosinophils by crossing the IL-5-overexpressing mice with SP-D(-/-) mice. Together, these studies support the conclusion that SP-D increases susceptibility to C. neoformans infection by promoting C. neoformans-driven pulmonary IL-5 and eosinophil infiltration.
Department of Cell Biology, Duke University Medical Center, Durham, North Carolina, USA.
Stephanie M
SM
Holmer
Kathy S
KS
Evans
Yohannes G
YG
Asfaw
Divey
D
Saini
Wiley A
WA
Schell
Julie G
JG
Ledford
Richard
R
Frothingham
Jo Rae
JR
Wright
Gregory D
GD
Sempowski
John R
JR
Perfect
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D003453:Cryptococcosis / Q000276:immunology* / Q000473:pathology*; D003455:Cryptococcus neoformans / Q000276:immunology*; D004195:Disease Models, Animal; D004802:Eosinophilia / Q000276:immunology*; D005260:Female; D015848:Interleukin-5 / Q000276:immunology*; D008168:Lung / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D037663:Pulmonary Surfactant-Associated Protein D / Q000172:deficiency / Q000276:immunology*
D015848:Interleukin-5; D037663:Pulmonary Surfactant-Associated Protein D