Transcriptomic evidence for modulation of host inflammatory responses during febrile Plasmodium falciparum malaria

被引：66

作者：

Tran, Tuan M. ^{[1
,2
]}

Jones, Marcus B. ^{[3
]}

Ongoiba, Aissata ^{[4
]}

Bijker, Else M. ^{[5
]}

Schats, Remko ^{[6
]}

Venepally, Pratap ^{[3
]}

Skinner, Jeff ^{[1
]}

Doumbo, Safiatou ^{[4
]}

Quinten, Edwin ^{[6
]}

Visser, Leo G. ^{[6
]}

Whalen, Elizabeth ^{[7
]}

Presnell, Scott ^{[7
]}

O'Connell, Elise M. ^{[8
]}

Kayentao, Kassoum ^{[4
]}

Doumbo, Ogobara K. ^{[4
]}

Chaussabel, Damien ^{[7
,9
]}

Lorenzi, Hernan ^{[10
]}

Nutman, Thomas B. ^{[8
]}

Ottenhoff, Tom H. M. ^{[6
]}

Haks, Marielle C. ^{[6
]}

Traore, Boubacar ^{[4
]}

Kirkness, Ewen F. ^{[3
]}

Sauerwein, Robert W. ^{[5
]}

Crompton, Peter D. ^{[1
]}

机构：

[1] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA

[2] Indiana Univ Sch Med, Dept Med, Div Infect Dis, Indianapolis, IN 46202 USA

[3] J Craig Venter Inst, Genom Med Grp, Rockville, MD USA

[4] Univ Sci Tech & Technol Bamako, Mali Int Ctr Excellence Res, Bamako, Mali

[5] Radboud Univ Nijmegen, Med Ctr, Dept Med Microbiol, Nijmegen, Netherlands

[6] Leiden Univ, Med Ctr, Dept Infect Dis, Leiden, Netherlands

[7] Benaroya Res Inst, Syst Immunol Div, Seattle, WA USA

[8] NIAID, Parasit Dis Lab, NIH, Bethesda, MD USA

[9] Sidra Med & Res Ctr, Doha, Qatar

[10] J Craig Venter Inst, Infect Dis Grp, Bethesda, MD USA

来源：

SCIENTIFIC REPORTS | 2016年 / 6卷

基金：

美国国家卫生研究院;

关键词：

DIFFERENTIAL EXPRESSION ANALYSIS; ACQUIRED-IMMUNITY; GENE-EXPRESSION; PROTECTION; COHORT;

D O I：

10.1038/srep31291

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Identifying molecular predictors and mechanisms of malaria disease is important for understanding how Plasmodium falciparum malaria is controlled. Transcriptomic studies in humans have so far been limited to retrospective analysis of blood samples from clinical cases. In this prospective, proof-of-principle study, we compared whole-blood RNA-seq profiles at pre- and post-infection time points from Malian adults who were either asymptomatic (n = 5) or febrile (n = 3) during their first seasonal PCR-positive P. falciparum infection with those from malaria-naive Dutch adults after a single controlled human malaria infection (n = 5). Our data show a graded activation of pathways downstream of pro-inflammatory cytokines, with the highest activation in malaria-naive Dutch individuals and significantly reduced activation in malaria-experienced Malians. Newly febrile and asymptomatic infections in Malians were statistically indistinguishable except for genes activated by pro-inflammatory cytokines. The combined data provide a molecular basis for the development of a pyrogenic threshold as individuals acquire immunity to clinical malaria.

引用

页数：12

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