摘要Background : Staphylococcus aureus can cause serious infections by secreting many superantigen exotoxins in "carrier" or "pathogenic" states. HLA DQ and HLA DR humanized mice have been used as a small animal model to study the role of two molecules during S. aureus infection. However, the contribution of HLA DP to S. aureus infection is unknown yet.Methods : In this study, we have produced HLA DP401 and HLA DRA0101 humanized mice by microinjection of C57BL/6J zygotes. Neo- floxed IAβ +/? mice were crossbred with Ella- Cre and further crossbred with HLA DP401 or HLA- DRA0101 humanized mice. After several rounds of traditional crossbreeding, we finally obtained HLA DP401- IAβ ?/? and HLA DRA- IAβ ?/? humanized mice, in which human DP401 or DRA0101 molecule was introduced into IAβ ?/? mice deficient in endogenous murine MHC class Ⅱ molecules. A transnasal infection murine model of S. aureus pneumonia was induced in the humanized mice by administering 2 × 108 CFU of S. aureus Newman dropwise into the nasal cavity. The immune responses and histopathology changes were further assessed in lungs in these infected mice. Results : We evaluated the local and systemic effects of S. aureus delivered intranasally in HLA DP401 - IAβ ?/? and HLA DRA- IAβ?/? transgenic mice. S. aureus Newman infection significantly increased the mRNA level of IL 12p40 in lungs in humanized mice. An increase in IFN- γ and IL- 6 protein was observed in HLA DRA- IAβ ?/? mice. We observed a declining trend in the percentage of F4/80 + macrophages in lungs in HLA DP401- IAβ ?/? mice and a decreasing ratio of CD4 + to CD8 + T cells in lungs in IAβ?/? mice and HLA DP401- IAβ ?/? mice. A decreasing ratio of Vβ3 + to Vβ8 + T cells was also found in the lymph node of IAβ ?/? mice and HLA DP401- IAβ ?/? mice. S. aureus Newman infection resulted in a weaker pathological injury in lungs in IAβ ?/? genetic background mice.Conclusion : These humanized mice will be an invaluable mouse model to resolve the pathological mechanism of S. aureus pneumonia and study what role DP molecule plays in S. aureus infection.