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

doi:10.1016/j.isci.2022.104384

Contrasting behavior between the three human monocyte subsets in dengue pathophysiology

iScience. 2022 May 10;25(6):104384. doi: 10.1016/j.isci.2022.104384. eCollection 2022 Jun 17.

Authors

Deepti Maheshwari¹, Keshav Saini¹, Prabhat Singh¹, Mohit Singla², Kaustuv Nayak¹, Charu Aggarwal¹, Yadya M Chawla¹, Prashant Bajpai¹, Manpreet Kaur¹, Sivaram Gunisetty³, Christiane S Eberhardt⁴, Rajni Nyodu¹, Kathryn Moore^{3

5

6}, Mehul S Suthar^{3

4

5

6}, Guruprasad R Medigeshi⁷, Evan Anderson³, Rakesh Lodha², Sushil K Kabra², Rafi Ahmed^{4

5}, Anmol Chandele¹, Kaja Murali-Krishna^{1

3

5}

Affiliations

¹ ICGEB-Emory Vaccine Center, International Center for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi, India.
² Department of Pediatrics, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India.
³ Department of Pediatrics, Division of Infectious Disease, Emory University School of Medicine, Atlanta, GA, USA.
⁴ Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, USA.
⁵ Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, USA.
⁶ Yerkes National Primate Research Center, Atlanta, GA, USA.
⁷ Translational Health Science and Technology Institute, Faridabad, Haryana, India.

Abstract

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.

Keywords: Immunology; Omics; Virology.

Grants and funding

P51 OD011132/OD/NIH HHS/United States