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Role of the Heme Oxygenase-1 (HO-1) In Modulating Inflammation After Insect Bites
Heme Oxygenase-1 Induction by Blood-Feeding Arthropods Controls Skin Inflammation and Promotes Disease Tolerance.
December 15th, 2020
1:00 – 2:00 PM EST
10:00 – 11:00 AM PST
Thiago Soares de Souza Vieira, PhD
National Institutes of Allergies and Infectious Diseases, NIH
Thiago Vieira acquired his Bachelors in Microbiology and Immunology and PhD in Immunology and Inflammation from the Federal University of Rio de Janeiro. Subsequently, Thiago came to the United States in 2016 as a Postdoctoral Associate at University of Massachusetts Medical School and since 2017 has been a Postdoctoral fellow at NIAID in the NIH and most recently, 2020, a faculty member at Foundation of Advanced Education in Sciences.
- Increase of Heme Oxygenase-1 (HO-1) protein translation is a widespread host skin response to the bite of many vectors of disease.
- ECL and Total Protein Normalization in Western Blots as a tool to evaluate changes in protein expression produced by insect bites using the Azure Biosystems c600 imager.
- Use of confocal imaging and flow cytometry analysis to reveal the role of extravascular red blood cell (RBC) internalization in the production of HO-1.
- Importance of HO-1 to control tolerance of the host to both transmitted pathogens and tissue damage supported by full knockdown model and in vivo enzymatic inhibition of the enzyme.
Figure: HO-1 Is Induced in Host Skin in Response to Blood-Feeding Arthropod Vectors
HO-1 western blot from skin tissue lysate (STL) of ears exposed to 10 Lutzomyia longipalpis or Phlebotomus duboscqi sand flies, 10 Aedes aegypti or Anopheles gambiae mosquitoes, 3 Ornithodoros turicata ticks, or poked 10 times with a 32-gauge needle. Naïve unbitten ears were used as negative control; and spleen, positive control. Hsp90 was used as loading control. Image was acquired by chemiluminescence using Azure c600. (n = 4–6 pooled ears).
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, is involved with HO-1 production after sand fly bites.
Importantly, we also 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. Accordingly, carbon monoxide – 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.
- Virology: Dengue Fever, Zika Fever, Yellow Fever, Chikungunya, West Nile Fever and other encephalitis, several Equine Encephalitis.
- Parasitology: Leishmaniasis, Malaria, Filariasis.
- Immunology: inflammation, macrophage migration.
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