Single-cell analyses and host genetics highlight the role of innate immune cells in COVID-19 severity

被引：38

作者：

Edahiro, Ryuya ^{[1
,2
]}

Shirai, Yuya ^{[1
,2
,3
]}

Takeshima, Yusuke ^{[4
]}

Sakakibara, Shuhei ^{[5
]}

Yamaguchi, Yuta ^{[2
,6
]}

Murakami, Teruaki ^{[2
,6
]}

Morita, Takayoshi ^{[2
,6
]}

Kato, Yasuhiro ^{[2
,6
]}

Liu, Yu-Chen ^{[7
]}

Motooka, Daisuke ^{[7
,8
,9
]}

Naito, Yoko ^{[1
,8
]}

Takuwa, Ayako ^{[7
]}

Sugihara, Fuminori ^{[10
,11
]}

Tanaka, Kentaro ^{[8
]}

Wing, James B. ^{[12
,13
]}

Sonehara, Kyuto ^{[1
,9
,14
,15
]}

Tomofuji, Yoshihiko ^{[1
,9
,14
]}

Namkoong, Ho ^{[16
]}

Tanaka, Hiromu ^{[17
]}

Lee, Ho ^{[17
]}

Fukunaga, Koichi ^{[17
]}

Hirata, Haruhiko ^{[2
]}

Takeda, Yoshito ^{[2
]}

Okuzaki, Daisuke ^{[7
,8
,9
,13
,18
]}

Kumanogoh, Atsushi ^{[2
,6
,9
,13
,18
]}

Okada, Yukinori ^{[1
,3
,9
,13
,14
,15
]}

Wang, Qingbo S. ^{[1
,3
]}

Edahiro, Ryuya ^{[1
,2
]}

Namkoong, Ho ^{[16
]}

Hasegawa, Takanori ^{[19
]}

Shirai, Yuya ^{[1
,2
,3
]}

Sonehara, Kyuto ^{[1
,9
,14
,15
]}

Tanaka, Hiromu ^{[17
]}

Lee, Ho ^{[17
]}

Saiki, Ryunosuke ^{[20
]}

Hyugaji, Takayoshi ^{[21
]}

Shimizu, Eigo ^{[21
]}

Katayama, Kotoe ^{[21
]}

Kanai, Masahiro ^{[22
]}

Naito, Tatsuhiko

Sasa, Noah ^{[1
,23
]}

Yamamoto, Kenichi ^{[1
,3
,24
]}

Kato, Yasuhiro ^{[2
,6
]}

Morita, Takayoshi ^{[2
,6
]}

Takahashi, Kazuhisa ^{[25
,26
]}

Harada, Norihiro ^{[25
,26
]}

Naito, Toshio ^{[26
,27
]}

Hiki, Makoto ^{[26
,28
,29
]}

Matsushita, Yasushi ^{[26
,30
]}

Takagi, Haruhi ^{[25
,26
]}

机构：

[1] Osaka Univ, Dept Stat Genet, Grad Sch Med, Suita, Osaka, Japan

[2] Osaka Univ, Dept Resp Med & Clin Immunol, Grad Sch Med, Suita, Osaka, Japan

[3] Osaka Univ, Lab Stat Immunol, Immunol Frontier Res Ctr WPI IFReC, Suita, Osaka, Japan

[4] Osaka Univ, Lab Expt Immunol, Immunol Frontier Res Ctr WPI IFReC, Suita, Osaka, Japan

[5] Osaka Univ, Lab Immune Regulat, Immunol Frontier Res Ctr WPI IFReC, Suita, Osaka, Japan

[6] Osaka Univ, Dept Immunopathol, Immunol Frontier Res Ctr WPI IFReC, Suita, Osaka, Japan

[7] Osaka Univ, WPI Immunol Frontier Res Ctr, Lab Human Immunol Single Cell Genom, Suita, Osaka, Japan

[8] Osaka Univ, Microbial Dis Res Inst, Genome Informat Res Ctr, Suita, Osaka, Japan

[9] Osaka Univ, Inst Open & Transdisciplinary Res Initiat, Integrated Frontier Res Med Sci Div, Suita, Osaka, Japan

[10] Osaka Univ, Core Instrumentat Facil, Immunol Frontier Res Ctr, Suita, Osaka, Japan

[11] Osaka Univ, Microbial Dis Res Inst, Suita, Osaka, Japan

[12] Osaka Univ, Immunol Frontier Res Ctr, Lab Human Immunol Single Cell Immunol, Suita, Osaka, Japan

[13] Osaka Univ, Ctr Infect Dis Educ & Res CiDER, Suita, Osaka, Japan

[14] RIKEN Ctr Integrat Med Sci, Lab Syst Genet, Yokohama, Kanagawa, Japan

[15] Univ Tokyo, Grad Sch Med, Dept Genome Informat, Tokyo, Japan

[16] Keio Univ, Dept Infect Dis, Sch Med, Tokyo, Japan

[17] Keio Univ, Dept Med, Sch Med, Div Pulm Med, Tokyo, Japan

[18] Osaka Univ, Japan Agcy Med Res & Dev Core Res Evolut Sci & Te, Osaka, Japan

[19] Tokyo Med & Dent Univ, M&D Data Sci Ctr, Tokyo, Japan

[20] Kyoto Univ, Dept Pathol & Tumor Biol, Kyoto, Japan

[21] Univ Tokyo, Inst Med Sci, Ctr Human Genome, Div Hlth Med Intelligence, Tokyo, Japan

[22] Harvard Med Sch, Dept Biomed Informat, Boston, MA USA

[23] Osaka Univ, Grad Sch Med, Dept Otorhinolaryngol Head & Neck Surg, Suita, Osaka, Japan

[24] Osaka Univ, Grad Sch Med, Dept Pediat, Suita, Osaka, Japan

[25] Juntendo Univ, Dept Resp Med, Fac Med, Tokyo, Japan

[26] Grad Sch Med, Tokyo, Japan

[27] Juntendo Univ, Fac Med, Dept Gen Med, Tokyo, Japan

[28] Juntendo Univ, Fac Med, Dept Emergency & Disaster Med, Tokyo, Japan

[29] Juntendo Univ, Fac Med, Dept Cardiovasc Biol & Med, Tokyo, Japan

[30] Juntendo Univ, Fac Med, Dept Internal Med & Rheumatol, Tokyo, Japan

[31] Juntendo Univ, Atopy Allergy Res Ctr, Grad Sch Med, Tokyo, Japan

[32] Keio Univ, Dept Emergency & Crit Care Med, Sch Med, Tokyo, Japan

[33] Keio Univ, Dept Anesthesiol, Sch Med, Tokyo, Japan

[34] Keio Univ, Dept Lab Med, Sch Med, Tokyo, Japan

[35] Keio Univ, Dept Med, Sch Med, Div Gastroenterol & Hepatol, Tokyo, Japan

[36] Keio Univ, Ctr Hlth, Tokyo, Japan

[37] Saitama Cardiovasc & Resp Ctr, Dept Resp Med, Kumagaya, Saitama, Japan

[38] Japan Community Hlth Care Org JCHO Saitama Med Ct, Dept Internal Med, Saitama, Japan

[39] Tokyo Womens Med Univ, Dept Resp Med, Tokyo, Japan

[40] Tokyo Womens Med Univ, Dept Gen Med, Tokyo, Japan

[41] Tokyo Med & Dent Univ Hosp Med, Clin Res Ctr, Tokyo, Japan

[42] Tokyo Med & Dent Univ Hosp Med, Dept Med Informat, Tokyo, Japan

[43] Tokyo Med & Dent Univ, Resp Med, Tokyo, Japan

[44] Tokyo Med & Dent Univ Hosp Med, Clin Lab, Tokyo, Japan

[45] Kawasaki Municipal Ida Hosp, Dept Internal Med, Kawasaki, Kanagawa, Japan

[46] Osaka Saiseikai Nakatsu Hosp, Dept Resp Med, Osaka, Japan

[47] Osaka Saiseikai Nakatsu Hosp, Dept Infect Control, Osaka, Japan

[48] Tosei Gen Hosp, Dept Infect Dis, Seto, Japan

[49] Tosei Gen Hosp, Dept Resp Med & Allergy, Seto, Japan

[50] Kansai Med Univ, Dept Emergency & Crit Care Med, Gen Med Ctr, Moriguchi, Osaka, Japan

来源：

NATURE GENETICS | 2023年 / 55卷 / 05期

关键词：

SUBSETS; PACKAGE; STATE; MILD;

D O I：

10.1038/s41588-023-01375-1

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Peripheral blood mononuclear cells from 73 Japanese patients with coronavirus disease 2019 (COVID-19) and 75 healthy controls were analyzed using single-cell transcriptomics. Combining these data with genotyping data highlights the interplay between host genetics and the immune response in modulating disease severity. Mechanisms underpinning the dysfunctional immune response in severe acute respiratory syndrome coronavirus 2 infection are elusive. We analyzed single-cell transcriptomes and T and B cell receptors (BCR) of >895,000 peripheral blood mononuclear cells from 73 coronavirus disease 2019 (COVID-19) patients and 75 healthy controls of Japanese ancestry with host genetic data. COVID-19 patients showed a low fraction of nonclassical monocytes (ncMono). We report downregulated cell transitions from classical monocytes to ncMono in COVID-19 with reduced CXCL10 expression in ncMono in severe disease. Cell-cell communication analysis inferred decreased cellular interactions involving ncMono in severe COVID-19. Clonal expansions of BCR were evident in the plasmablasts of patients. Putative disease genes identified by COVID-19 genome-wide association study showed cell type-specific expressions in monocytes and dendritic cells. A COVID-19-associated risk variant at the IFNAR2 locus (rs13050728) had context-specific and monocyte-specific expression quantitative trait loci effects. Our study highlights biological and host genetic involvement of innate immune cells in COVID-19 severity.

引用

页码：753 / +

页数：32

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