# Implicating a previously unknown Dectin1-RIPK2-CARD9 signaling in providing resistance against Leishmania major infection

> **NIH NIH R01** · UNIVERSITY OF IOWA · 2021 · $512,544

## Abstract

PROJECT SUMMARY
Pathogen recognition receptors and their associated adaptors are essential for the prompt detection of
pathogens and the subsequent initiation of effective host responses and restoration of homeostasis. Over the
last decade, Nod-like receptors (NLRs) have been on the forefront of innate immune research, and several
groundbreaking studies have been published, to which my research has contributed. Leishmania spp. are
parasites with global health importance, yet the role of NLRs and their adaptors during Leishmania spp.
infection has been an understudied area.
Receptor interacting protein kinase 2 (RIPK2) is an essential adaptor downstream of cytoplasmic sensors
NLRC1 and NLRC2, and play an important role in a wide variety of clinical settings including bacterial, viral and
fungal infections, as well as non-infectious inflammatory diseases such as multiple sclerosis, inflammatory
bowel disease and metabolic diseases. However, the role of RIPK2 during cutaneous leishmaniasis remain
unknown. In this grant, we propose to investigate the precise cellular and molecular mechanisms involving
RIPK2 during Leishmania major (L. major)-induced cutaneous disease. Our preliminary work has already
elucidated several exciting features of the role of RIPK2 during L. major infection. We found that RIPK2-
deficient mice are highly susceptible to L. major infection. Unexpectedly, mice deficient in NLRC2 or both
NLRC1/NLRC2 are dispensable in L. major infection suggesting a novel sensor that function upstream of
RIPK2. Moreover, RIPK2 interacted with CARD9 to provide protection against L. major. Based on these
preliminary data, we propose that a novel Dectin-1/RIPK2/CARD9 signaling axis modulates anti-leishmanial
immunity.
Successful completion of this project will yield a better understanding of RIPK2 biology in general, unveil a
novel pathway involving RIPK2 in signal transduction, and potentially identify therapeutic targets to ameliorate
Leishmania spp.-associated pathology.
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## Key facts

- **NIH application ID:** 10092450
- **Project number:** 1R01AI155425-01
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Prajwal Gurung
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $512,544
- **Award type:** 1
- **Project period:** 2021-03-24 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10092450

## Citation

> US National Institutes of Health, RePORTER application 10092450, Implicating a previously unknown Dectin1-RIPK2-CARD9 signaling in providing resistance against Leishmania major infection (1R01AI155425-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10092450. Licensed CC0.

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