Heme Oxygenase-1 Induction by Blood-Feeding Arthropods Controls Skin Inflammation and Promotes Disease Tolerance
Hematophagous vectors lacerate host skin and capillaries to acquire a blood meal, resulting in leakage of red blood cells (RBCs) and inflammation. Here, we show that heme oxygenase-1 (HO-1), a pleiotropic cytoprotective isoenzyme that mitigates heme-mediated tissue damage, is induced after bites of...
Saved in:
Published in: | Cell reports (Cambridge) 2020-10, Vol.33 (4), p.108317-108317, Article 108317 |
---|---|
Main Authors: | , , , , , , , , , , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
Summary: | Hematophagous vectors lacerate host skin and capillaries to acquire a blood meal, resulting in leakage of red blood cells (RBCs) and inflammation. Here, we show that heme oxygenase-1 (HO-1), a pleiotropic cytoprotective isoenzyme that mitigates heme-mediated tissue damage, is induced after bites of sand flies, mosquitoes, and ticks. Further, we demonstrate that erythrophagocytosis by macrophages, including a skin-residing CD163+CD91+ professional iron-recycling subpopulation, produces HO-1 after bites. Importantly, we establish that global deletion or transient inhibition of HO-1 in mice increases inflammation and pathology following Leishmania-infected sand fly bites without affecting parasite number, whereas CO, an end product of the HO-1 enzymatic reaction, suppresses skin inflammation. This indicates that HO-1 induction by blood-feeding sand flies promotes tolerance to Leishmania infection. Collectively, our data demonstrate that HO-1 induction through erythrophagocytosis is a universal mechanism that regulates skin inflammation following blood feeding by arthropods, thus promoting early-stage disease tolerance to vector-borne pathogens.
[Display omitted]
•Blood-feeding arthropod bites damage blood vessels, causing RBC leakage into tissue•Extravascular RBCs are ingested by skin macrophages, leading to production of HO-1•Inhibition of HO-1 enhances inflammation and promotes tissue damage•HO-1 production after Leishmania-infected sand fly bites promotes disease tolerance
Vector-borne diseases afflict millions of people worldwide. DeSouza-Vieira et al. demonstrate that blood-feeding arthropods induce HO-1 in skin macrophages that ingest extravascular erythrocytes from damaged vessels. Without HO-1, sand fly transmission of Leishmania led to aggravated cutaneous leishmaniasis pathology without affecting the parasites, indicating that HO-1 production promotes disease tolerance. |
---|---|
ISSN: | 2211-1247 2211-1247 |
DOI: | 10.1016/j.celrep.2020.108317 |