ORIGINAL RESEARCH article
Front. Cell. Infect. Microbiol.
Sec. Microbes and Innate Immunity
Volume 15 - 2025 | doi: 10.3389/fcimb.2025.1670259
This article is part of the Research TopicEmerging Mechanisms of Host-Pathogen Interactions and immune responsesView all 11 articles
Elucidation of neutrophils mediated effect of MMP-2 on lung epithelial cells; implications for acute respiratory distress syndrome and severe dengue pathogenesis
Provisionally accepted
Rituraj Niranjan1*
Khashpatika Ganesh#2Anupama Sunil2
Vyshali Murugasamy2Pitchavel Vidhyapriya2
Muthukumaravel Subramanian2
Dr Ashwani Kumar2- 1Indian Institute of Technology Kanpur, Kanpur, India
- 2ICMR - Vector Control Research Centre, Indira Nagar, India
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ABSTRACT: Dengue is a vector borne viral fever which is spread by the bites of Aedes mosquitoes. MMPs play a significant role in the beginning and development of dengue pathogenesis, but their precise functions with respect to neutrophil's associated lung pathology are not understood. In the present study, we for the first-time report that, in vitro cultured neutrophils secrete MMP-2 in response to dengue virus NS1 antigens in culture medium (the secretome). We have assessed the effect of neutrophil's secretome on the apoptosis of A549 lung epithelial cells and found that it causes their death. This suggested that neutrophils cause apoptosis of lung epithelial cells via MMP-2 mediated mechanisms. The exposure of purified MMP-2 protein has also caused cell death of A549 epithelial cells by increasing mRNA expression pattern of apoptotic genes. Atorvastatin (10µM) treatment attenuated the change in the release of MMP-2 and further decreased the apoptosis of lung epithelial cells. Interestingly it was seen that MMP-14 alone and NS1 antigen aloe does not cause the apoptosis of lung epithelial cells ruling out their direct involvements. The interactions of CD31 positive neutrophils in lungs and MMP-2 expression was also found in NS1 injected mice supporting their role in in vivo situations. In conclusion, this study suggests that, interaction of NS1 activated neutrophils with the alveolar epithelial cells participate in the lung pathogenesis involved in the acute respiratory distress syndrome (ARDS) in severe dengue disease. The present results are encouraging; however, further investigations are required to clarify the findings.
Keywords: Neutrophils, Dengue pathogenesis, MMP-2, Acute Respiratory Distress Syndrome, lung epithelial cells
Received: 21 Jul 2025; Accepted: 01 Sep 2025.
Copyright: © 2025 Niranjan, Ganesh#, Sunil, Murugasamy, Vidhyapriya, Subramanian and Kumar. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Rituraj Niranjan, Indian Institute of Technology Kanpur, Kanpur, India
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