# Innate inflammatory cells in leishmaniasis

> **NIH VA I01** · IOWA CITY VA MEDICAL CENTER · 2020 · —

## Abstract

The Leishmania spp. protozoa cause a group of diseases that are common in the many endemic
countries worldwide. These include Afghanistan and Iraq, countries where recent outbreaks of
leishmaniasis have initiated among US military personnel. The most common clinical forms of
leishmaniasis, and the most common causes of these outbreaks, are cutaneous leishmaniasis (CL)
due to Leishmania major, and visceral leishmaniasis (VL) caused by L. infantum or L. donovani.
 Leishmania are obligate intracellular parasites in mammals. Most parasites reside in
macrophages, where they replicate and survive long-term. Recent data show that neutrophils are the
first host cells to infiltrate and internalize parasites in the skin after the bite of an infected sand fly. The
passage of Leishmania through neutrophils before they are internalized by other phagocytes has
been cited as a means of paralyzing the microbicidal and antigen presenting functions of
macrophages and dendritic cells early in infection. During studies of human leishmaniasis we were
surprised to find a subset of neutrophils expressing class II MHC antigens and other markers of
antigen presenting cells (APCs) in chronic infection. MHCII+ PMNs also expressed PD-L1, a T cell
exhaustion receptor ligand, leading us to question a potential role in adaptive immunity. A further role
of neutrophils was implied by studies of mice lacking NLRP10, which developed prolonged, severe
cutaneous lesions but no change in their parasite load, suggesting that NLRP10 is critical for
resolution of a neutrophilic infiltrate that contributes to the manifestations of disease. These
observations led us to hypothesize that neutrophils contribute toward exacerbating or prolonging
symptomatic leishmaniasis, in a manner independent of leishmanicidal activity. We propose to
pursue these hypotheses by examining the following three aims.
Aim 1: The extent of neutrophil recruitment, and neutrophil phenotypes at the sites of
inflammation during murine leishmaniasis. Hypothesis: Unusual subsets of neutrophils are
recruited to the site of Leishmania spp. infection acutely, and through chronic phases of infection.
Aim 2: The development and functions of neutrophil subsets in Leishmania spp. infection.
Hypothesis: The dysfunctional immune responses observed in leishmaniasis, leading the host type 1
immune response astray from eradicating the parasite and curing disease, is amplified in part by
subsets of neutrophils expressing markers of APCs and/or T cell exhaustion partners.
Aim 3. The role of NLRP10 in resolution of neutrophil-dominated inflammatory lesions.
Hypothesis: Resolution of neutrophilic infiltration into the infection site, mediated by tissue-expressed
NLRP10, is needed for resolution of disease.

## Key facts

- **NIH application ID:** 9815310
- **Project number:** 5I01BX001983-06
- **Recipient organization:** IOWA CITY VA MEDICAL CENTER
- **Principal Investigator:** Mary E Wilson
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2013-10-01 → 2022-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9815310

## Citation

> US National Institutes of Health, RePORTER application 9815310, Innate inflammatory cells in leishmaniasis (5I01BX001983-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9815310. Licensed CC0.

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