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HLA<\/jats:italic> DQ<\/jats:italic> and HLA<\/jats:italic> DR<\/jats:italic> humanized mice have been used as a small animal model to study the role of two molecules during S. aureus<\/jats:italic> infection. However, the contribution of HLA<\/jats:italic> DP<\/jats:italic> to S. aureus<\/jats:italic> infection is unknown yet.<\/jats:p><\/jats:sec>Methods<\/jats:title>In this study, we have produced HLA<\/jats:italic> DP401<\/jats:italic> and HLA<\/jats:italic> DRA0101<\/jats:italic> humanized mice by microinjection of C57BL\/6J zygotes. Neo\u2010floxed IA\u03b2<\/jats:italic>+\/\u2212<\/jats:sup> mice were crossbred with Ella\u2010Cre and further crossbred with HLA<\/jats:italic> DP401<\/jats:italic> or HLA\u2010DRA0101 humanized mice. After several rounds of traditional crossbreeding, we finally obtained HLA DP401\u2010IA\u03b2<\/jats:italic>\u2212\/\u2212<\/jats:sup> and HLA DRA\u2010IA\u03b2<\/jats:italic>\u2212\/\u2212<\/jats:sup> humanized mice, in which human DP401<\/jats:italic> or DRA0101<\/jats:italic> molecule was introduced into IA\u03b2<\/jats:italic>\u2212\/\u2212<\/jats:sup> mice deficient in endogenous murine MHC class II molecules. A transnasal infection murine model of S. aureus<\/jats:italic> pneumonia was induced in the humanized mice by administering 2\u2009\u00d7\u2009108<\/jats:sup>\u2009CFU of S. aureus<\/jats:italic> Newman dropwise into the nasal cavity. The immune responses and histopathology changes were further assessed in lungs in these infected mice.<\/jats:p><\/jats:sec>Results<\/jats:title>We evaluated the local and systemic effects of S. aureus<\/jats:italic> delivered intranasally in HLA DP401<\/jats:italic>\u2010IA\u03b2<\/jats:italic>\u2212\/\u2212<\/jats:sup> and HLA DRA\u2010IA\u03b2\u2212\/\u2212<\/jats:sup> transgenic mice. S. aureus<\/jats:italic> Newman infection significantly increased the mRNA level of IL 12p40<\/jats:italic> in lungs in humanized mice. An increase in IFN\u2010\u03b3 and IL\u20106 protein was observed in HLA<\/jats:italic> DRA\u2010IA\u03b2<\/jats:italic>\u2212\/\u2212<\/jats:sup> mice. We observed a declining trend in the percentage of F4\/80+<\/jats:sup> macrophages in lungs in HLA<\/jats:italic> DP401\u2010IA\u03b2<\/jats:italic>\u2212\/\u2212<\/jats:sup> mice and a decreasing ratio of CD4+<\/jats:sup> to CD8+<\/jats:sup> T cells in lungs in IA\u03b2\u2212\/\u2212<\/jats:sup> mice and HLA DP401\u2010IA\u03b2<\/jats:italic>\u2212\/\u2212<\/jats:sup> mice. A decreasing ratio of V\u03b23+<\/jats:sup> to V\u03b28+<\/jats:sup> T cells was also found in the lymph node of IA\u03b2<\/jats:italic>\u2212\/\u2212<\/jats:sup> mice and HLA DP401\u2010IA\u03b2<\/jats:italic>\u2212\/\u2212<\/jats:sup> mice. S. aureus<\/jats:italic> Newman infection resulted in a weaker pathological injury in lungs in IA\u03b2<\/jats:italic>\u2212\/\u2212<\/jats:sup> genetic background mice.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>These humanized mice will be an invaluable mouse model to resolve the pathological mechanism of S. aureus<\/jats:italic> pneumonia and study what role DP molecule plays in S. aureus<\/jats:italic> infection.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ame2.12331","type":"journal-article","created":{"date-parts":[[2023,5,29]],"date-time":"2023-05-29T10:32:38Z","timestamp":1685356358000},"page":"585-597","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Characterization of genetic humanized mice with transgenic HLA DP401<\/scp> or DRA<\/scp> but deficient in endogenous murine MHC<\/scp> class II<\/scp> genes upon Staphylococcus aureus<\/i> pneumonia"],"prefix":"10.1002","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1291-5315","authenticated-orcid":false,"given":"Feng","family":"Li","sequence":"first","affiliation":[{"name":"Department of Laboratory Animal Science Shanghai Public Health Clinical Center Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bowen","family":"Niu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Animal Science Shanghai Public Health Clinical Center Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingling","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Animal Science Shanghai Public Health Clinical Center Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengmin","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Animal Science Shanghai Public Health Clinical Center Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Animal Science Shanghai Public Health Clinical Center Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boyin","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Laboratory Animal Science Shanghai Public Health Clinical Center Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuhua","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Laboratory Animal Science Shanghai Public Health Clinical Center Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixiang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Laboratory Animal Science Shanghai Public Health Clinical Center Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunhua","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Animal Science Shanghai Public Health Clinical Center Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohui","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Laboratory Animal Science Shanghai Public Health Clinical Center Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,5,29]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199808203390806"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200101043440102"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMe058023"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2014.04.007"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000703"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6968.2011.02262.x"},{"key":"e_1_2_10_8_1","first-page":"307","article-title":"Modelling infectious disease\u2014time to think outside the box? 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