Poor Innate and Adaptive Immune sensitization in dengue patients: A preliminary observational study on DHF/DSS as an infectious allergic condition



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Abstract

Dengue Fever is a major public health problem leading to serious morbidity and mortality worldwide. There are severe clinical conditions associated with Dengue Fever which may further lead to Dengue Haemorrhagic Fever or Dengue Shock syndrome. The  hypothesis of occurrence of Antibody Dependant Enhancement (ADE) is currently believed to be the immunological basis of DHF/DSS. However, some of the earlier studies and our current work, have shown that ADE might not be the sole cause of severe dengue. To establish its exact cause, so that therapeutic interventions can be made and recovery of patients be ensured, the present study was done. The blood samples were collected from dengue positive patients reporting to Sharda Hospital, India. A thin smear was prepared from 5µl of blood and stained using Leishman stain to count various immune cells. The serum was separated and subjected to RT-PCR to double ensure the presence of virus using Dengue specific primers. 100µl of serum was also taken for detecting Histamine levels using ELISA assay. Blood samples of severe dengue cases was also outsourced for electron microscopy to critically study the effect of virus on the various  immune cells. We observed that the major innate immune cells showed no immunogenic sensitization by the dengue virus but were permissive for infection and led to formation of neutrophil traps. Lymphocytes as gross adaptive immune cells showed elevation but without generating pathogen specific IgM antibodies. Granulocytes such as basophils have shown substantial enhancement pointing the symptoms more as allergic reactions rather than infectious outcomes. The serum histamine level was raised in all the severe patients of dengue. Present paper sensitizes the issue that DHF cases showing subcutaneous haemorrhages could be histamine induced allergy and stage of DSS could be a systemic anaphylaxis due hypersensitivity type 1 reactions. Paper sensitizes further studies in this direction through which use of anti-allergic, anti-histamine drugs could emerge as specific therapeutic intervention of DHF/DSS.

About the authors

Aarya Chitransh

Centre of Excellence in Virology and Immunology, Sharda University, Greater Noida, U.P., India

Email: 2023200035.aarya@dr.sharda.ac.in
ORCID iD: 0009-0005-6367-0532

M.Sc., Pursuing phd

Bennet Angel

Centre of Excellence in Virology and Immunology, Sharda University, Greater Noida, U.P., India

Email: bennet.angel@sharda.ac.in
ORCID iD: 0000-0002-9149-6974

Ph.D, Professor

India

Annette Angel

Centre of Excellence in Virology and Immunology, Sharda University, Greater Noida, U.P., India

Email: annette.angel@sharda.ac.in
ORCID iD: 0000-0003-4253-103X

Ph.D, Professor

India

Khushbu Kumari

Centre of Excellence in Virology and Immunology, Sharda University, Greater Noida, U.P., India

Email: khushbuthakur127@gmail.com
ORCID iD: 0009-0007-0191-1470

M.Sc., Pursuing phd

India

Ramesh Joshi

Dept of Life Science, Sharda School of Bioscience and Technology, Sharda University, U.P., India

Email: drrameshjoshi10@gmail.com
ORCID iD: 0000-0002-5775-5282

Ph.D, Professor

India

Shareef BM

Centre of Excellence in Virology and Immunology, Sharda University, Greater Noida, U.P., India

Email: shareef.biotech@gmail.com
ORCID iD: 0000-0003-1503-1881

Ph.D., Research Scientist

India

Bhawna Sharma

Centre of Excellence in Virology and Immunology, Sharda University, Greater Noida, U.P., India

Email: bhawnasharma032@gmail.com
ORCID iD: 0000-0003-4427-7047

Ph.D., Research Scientist

India

Jyoti Jethani

Indian Council of Medical Research, Ansari Nagar, New Delhi, India

Email: jethanijyoti31@gmail.com
ORCID iD: 0000-0003-1380-9143

Ph.D., Scientist B

India

Rashmi Chouhan

Shri Maneklal M Patel Institute of Sciences and Research, Kadi Sarva Vishwavidyalaya, Gandhinagar, Gujarat, India

Email: rashmi2583@gmail.com
ORCID iD: 0000-0002-4166-4677

Ph.D., Assistant Professor

India

Vinod Joshi

Centre of Excellence in Virology and Immunology, Sharda University, Greater Noida, U.P., India

Author for correspondence.
Email: vinod.joshi@sharda.ac.in
ORCID iD: 0000-0001-6599-5481

Ph.D, Professor

India, Centre of Excellence in Virology and Immunology, Sharda University, Greater Noida, U.P., India, 201310

References

  1. Angel, B., Angel, A., Joshi, V. Multiple dengue virus types harbored by individual mosquitoes. Acta tropica, 2015, Vol. 150, pp: 107–110. https://doi.org/10.1016/j.actatropica.2015.07.007
  2. Asha, K., Sharma-Walia, N. Virus and tumor microenvironment induced ER stress and unfolded protein response: from complexity to therapeutics. Oncotarget, 2018, Vol. 9, No.61, pp:31920–31936. https://doi.org/10.18632/oncotarget.25886.
  3. Bhatt, S., Gething, P. W., Brady, O. J., Messina, J. P., Farlow, A. W., Moyes, C. L., Drake, J. M., Brownstein, J. S., Hoen, A. G., Sankoh, O., Myers, M. F., George, D. B., Jaenisch, T., Wint, G. R., Simmons, C. P., Scott, T. W., Farrar, J. J., Hay, S. I. The global distribution and burden of dengue. Nature, 2013, Vol. 496, No. 7446, pp. 504–507. https://doi.org/10.1038/nature12060
  4. Elesela, S., Lukacs, N. W. Role of Mitochondria in Viral Infections. Life (Basel, Switzerland), 2021, Vol. 11, No. 3, pp. 232. https://doi.org/10.3390/life11030232.
  5. Espina, L. M., Valero, N. J., Hernández, J. M., Mosquera, J. A. Increased apoptosis and expression of tumor necrosis factor-alpha caused by infection of cultured human monocytes with dengue virus. American Journal of Tropical Medicine and Hygiene, 2003,Vol 68, No. 1, pp. 48–53. https://doi.org/10.4269/ajtmh.2003.68.48
  6. Halstead, S.B. Observations related to pathogenesis of dengue hemorrhagic fever. VI. Hypotheses and discussion. Yale Journal of Biology Medicine, 1970, Vol. 42, No. 5, pp:350-62. https://pubmed.ncbi.nlm.nih.gov/5419208/
  7. Halstead SB. Dengue Antibody-Dependent Enhancement: Knowns and Unknowns. Microbiology spectrum. 2014;Vol. 2, No. 6:pp: 10.1128. https://doi.org/10.1128/microbiolspec.AID-0022-2014
  8. King, A. D., Nisalak, A., Kalayanrooj, S., Myint, K. S., Pattanapanyasat, K., Nimmannitya, S., Innis, B. L. B cells are the principal circulating mononuclear cells infected by dengue virus. he Southeast Asian journal of tropical medicine and public health, 1999; Vol. 30, No. 4, pp: 718-28. https://pubmed.ncbi.nlm.nih.gov/10928366/
  9. Kou, Z., Quinn, M., Chen, H., Rodrigo, W. W., Rose, R. C., Schlesinger, J. J., & Jin, X. Monocytes, but not T or B cells, are the principal target cells for dengue virus (DV) infection among human peripheral blood mononuclear cells. Journal of Medical Virology. 2008, Vol. 80, No. 1, pp:134-46. https://doi.org/10.1002/jmv.21051
  10. Lee, Y. R., Kuo, S. H., Lin, C. Y., Fu, P. J., Lin, Y. S., Yeh, T. M., Liu, H. S. Dengue virus-induced ER stress is required for autophagy activation, viral replication, and pathogenesis both in vitro and in vivo. Scientific Reports, 2018;Vol. 8, No. 1, pp:489. https://doi.org/10.1038/s41598-017-18909-3
  11. Libraty, D. H., Pichyangkul, S., Ajariyakhajorn, C., Endy, T. P., Ennis, F. A. Human dendritic cells are activated by dengue virus infection: enhancement by gamma interferon and implications for disease pathogenesis. Journal of Virology, 2001, Vol. 75, No. 8, pp:3501-3508. https://doi.org/10.1128/JVI.75.8.3501-3508.2001
  12. Ngwe Tun, M. M., Thant, K. Z., Inoue, S., Kurosawa, Y., Lwin, Y. Y., Lin, S., Aye, K. T., Thet Khin, P., Myint, T., Htwe, K., Mapua, C. A., Natividad, F. F., Hirayama, K., Morita, K. Serological characterization of dengue virus infections observed among dengue hemorrhagic fever/dengue shock syndrome cases in upper Myanmar. Journal of Medical Virology, 2013, Vol. 85, No. 7, pp:1258-1266. https://doi.org/10.1002/jmv.23577
  13. Pang, X., Zhang, R., Cheng, G. Progress towards understanding the pathogenesis of dengue hemorrhagic fever. Virology Sinica, 2017, Vol. 32, No. 1, pp:16-22. https://doi.org/10.1007/s12250-016-3855-9
  14. Shrivastava, G., Valenzuela Leon, P. C., Calvo, E. Inflammasome Fuels Dengue Severity. Frontiers in Cellular and Infection Microbiology, 2020, Vol. 10, pp:489. https://doi.org/10.3389/fcimb.2020.00489
  15. Shu, P. Y., Chen, L. K., Chang, S. F., Yueh, Y. Y., Chow, L., Chien, L. J., Chin, C., Lin, T. H., Huang, J. H. Dengue NS1-specific antibody responses: isotype distribution and serotyping in patients with Dengue fever and Dengue hemorrhagic fever. Journal of Medical Virology, 2000, Vol. 62, No. 2, pp:224-32. https://doi.org/10.1002/1096-9071(200010)62:2<224::aid-jmv14>3.0.co;2-c
  16. Silveira, G. F., Wowk, P. F., Cataneo, A. H. D., Dos Santos, P. F., Delgobo, M., Stimamiglio, M. A., Lo Sarzi, M., Thomazelli, A. P. F. S., Conchon-Costa, I., Pavanelli, W. R., Antonelli, L. R. V., Báfica, A., Mansur, D. S., Dos Santos, C. N. D., Bordignon, J.Human T Lymphocytes Are Permissive for Dengue Virus Replication. Journal of Virology, 2018, Vol. 92, No. 10, pp:e02181-17. https://doi.org/10.1128/JVI.02181-17
  17. Srikiatkhachorn, A. Plasma leakage in dengue haemorrhagic fever. Thrombosis and haemostasis., 2009, Vol. 102, No. 6, pp:1042-49. https://doi.org/10.1160/TH09-03-0208
  18. Thaker, S. K., Ch'ng, J., Christofk, H. R. Viral hijacking of cellular metabolism. BMC Biology, 2019, Vol 17, No. 1, pp:59. https://doi.org/10.1186/s12915-019-0678-9
  19. Vervaeke, P., Vermeire, K., Liekens, S. Endothelial dysfunction in dengue virus pathology. Reviews in Medical Virology, 2015, Vol 25, No. 1, pp:50-67. https://doi.org/10.1002/rmv.1818

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Copyright (c) Chitransh A., Angel B., Angel A., Kumari K., Joshi R., BM S., Sharma B., Jethani J., Chouhan R., Joshi V.

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