Contrasting behavior between the three human monocyte subsets in dengue pathophysiology
Deepti Maheshwari,
Keshav Saini,
Prabhat Singh,
Mohit Singla,
Kaustuv Nayak,
Charu Aggarwal,
Yadya M. Chawla,
Prashant Bajpai,
Manpreet Kaur,
Sivaram Gunisetty,
Christiane S. Eberhardt,
Rajni Nyodu,
Kathryn Moore,
Mehul S. Suthar,
Guruprasad R. Medigeshi,
Evan Anderson,
Rakesh Lodha,
Sushil K. Kabra,
Rafi Ahmed,
Anmol Chandele,
Kaja Murali-Krishna
Affiliations
Deepti Maheshwari
ICGEB-Emory Vaccine Center, International Center for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi, India
Keshav Saini
ICGEB-Emory Vaccine Center, International Center for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi, India
Prabhat Singh
ICGEB-Emory Vaccine Center, International Center for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi, India
Mohit Singla
Department of Pediatrics, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India
Kaustuv Nayak
ICGEB-Emory Vaccine Center, International Center for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi, India
Charu Aggarwal
ICGEB-Emory Vaccine Center, International Center for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi, India
Yadya M. Chawla
ICGEB-Emory Vaccine Center, International Center for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi, India
Prashant Bajpai
ICGEB-Emory Vaccine Center, International Center for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi, India
Manpreet Kaur
ICGEB-Emory Vaccine Center, International Center for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi, India
Sivaram Gunisetty
Department of Pediatrics, Division of Infectious Disease, Emory University School of Medicine, Atlanta, GA, USA
Christiane S. Eberhardt
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, USA
Rajni Nyodu
ICGEB-Emory Vaccine Center, International Center for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi, India
Kathryn Moore
Department of Pediatrics, Division of Infectious Disease, Emory University School of Medicine, Atlanta, GA, USA; Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, USA; Yerkes National Primate Research Center, Atlanta, GA, USA
Mehul S. Suthar
Department of Pediatrics, Division of Infectious Disease, Emory University School of Medicine, Atlanta, GA, USA; Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, USA; Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, USA; Yerkes National Primate Research Center, Atlanta, GA, USA
Guruprasad R. Medigeshi
Translational Health Science and Technology Institute, Faridabad, Haryana, India
Evan Anderson
Department of Pediatrics, Division of Infectious Disease, Emory University School of Medicine, Atlanta, GA, USA
Rakesh Lodha
Department of Pediatrics, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India
Sushil K. Kabra
Department of Pediatrics, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India
Rafi Ahmed
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, USA; Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, USA
Anmol Chandele
ICGEB-Emory Vaccine Center, International Center for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi, India; Corresponding author
Kaja Murali-Krishna
ICGEB-Emory Vaccine Center, International Center for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi, India; Department of Pediatrics, Division of Infectious Disease, Emory University School of Medicine, Atlanta, GA, USA; Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, USA; Corresponding author
Summary: Monocytes are known to play a critical role in dengue pathophysiology. However, which monocyte subset expresses what inflammatory mediator(s) and what transcriptional features distinguish each of the monocyte subset in vivo remain poorly understood. In this study we provide a detailed transcriptional analysis of the three human monocyte subsets in healthy children and in children with dengue febrile illness. Notably, we found that the CD14+ CD16high intermediate monocyte subset from dengue patients highly upregulated key genes involved in mediating inflammation, endothelial dysfunction, vascular permeability, tissue extravasation, and clot prevention compared to healthy children. The CD14+CD16low classical monocytes shared some of these features. These two subsets increased massively in patients with severe dengue. By contrast, the CD14−CD16high nonclassical monocyte subset upregulated key genes involved in vasoconstriction, endothelial barrier stability, and are involved in endothelial patrolling while showing a significant decline from circulation. These findings improve our understanding of monocyte responses in dengue.
