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Clin Exp Allergy. 2019 Dec 13. doi: 10.1111/cea.13549. [Epub ahead of print]

Chronic infection with a tissue-invasive helminth attenuates sublethal anaphylaxis and reduces granularity and number of mast cells.

Author information

1
Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
2
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA.
3
Biomedical Instrumentation Center, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.

Abstract

BACKGROUND:

Immunoglobulin E (IgE)-mediated anaphylaxis is a potentially fatal condition in which allergy effector cells rapidly discharge pre-formed inflammatory mediators. Treatments that address the immune component of allergic anaphylaxis are inadequate. Helminths have been previously shown to suppress effector cell function; however, their ability to treat pre-existing allergy remains unclear.

OBJECTIVE:

To evaluate the ability of chronic helminth infection to protect against anaphylaxis in previously sensitized mice.

METHODS:

A sublethal model of anaphylaxis was used, in which BALB/c mice were sensitized by three intraperitoneal (i.p.) injections of OVA/alum. Temperature drop was then monitored after systemic OVA challenge in uninfected mice and in mice infected chronically with Litomosoides sigmodontis, a tissue-invasive filarial nematode.

RESULTS:

Litomosoides sigmodontis-infected mice exhibited significantly lower serum levels of mMCP-1 and were less hypothermic at 30-minute post-challenge compared to uninfected OVA-challenged controls. Characterization of anaphylaxis revealed that FcԑR1 and mast cells were required for hypothermia and elevated serum mMCP-1. OVA-IgE and OVA-IgG1 serum levels were not significantly altered by L sigmodontis infection, and experiments with IL-10-/- mice demonstrated that IL-10 was not required for protection against anaphylaxis. However, peritoneal mast cell numbers were significantly lower in infected mice, and those that were present exhibited decreased granularity by flow cytometry and marked depletion of intracytoplasmic granules by light microscopy. Mast cells from infected mice had lower expression of the activation markers CD200R and CD63 and contained significantly lower basal stores of histamine.

CONCLUSIONS:

Chronic L sigmodontis infection protects against anaphylaxis, likely due to reduction in mast cell numbers and depletion of pre-formed inflammatory mediators in remaining mast cells.

KEYWORDS:

allergy; anaphylaxis; helminth; immunoglobulin E; mast cells; parasites

PMID:
31834940
DOI:
10.1111/cea.13549

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