Elevated Systemic Levels of Eosinophil, Neutrophil, and Mast Cell Granular Proteins in Strongyloides Stercoralis Infection that Diminish following Treatment

Abstract

Infection with the helminth parasite Strongyloides stercoralis (Ss) is commonly clinically asymptomatic that is often accompanied by peripheral eosinophilia. Granulocytes are activated during helminth infection and can act as immune effector cells. Plasma levels of eosinophil and neutrophil granular proteins convey an indirect measure of granulocyte degranulation and are prominently augmented in numerous helminth-infected patients. In this study, we sought to examine the levels of eosinophil, neutrophil, and mast cell activation-associated granule proteins in asymptomatic Ss infection and to understand their kinetics following anthelmintic therapy. To this end, we measured the plasma levels of eosinophil cationic protein, eosinophil-derived neurotoxin, eosinophil peroxidase, eosinophil major basic protein, neutrophil elastase, myeloperoxidase, neutrophil proteinase-3, mast cell tryptase, leukotriene C4, and mast cell carboxypeptidase-A3 in individuals with asymptomatic Ss infection or without Ss infection [uninfected (UN)]. We also estimated the levels of all of these analytes in infected individuals following definitive treatment of Ss infection. We demonstrated that those infected individuals have significantly enhanced plasma levels of eosinophil cationic protein, eosinophil-derived neurotoxin, eosinophil peroxidase, eosinophil major basic protein, elastase, myeloperoxidase, mast cell tryptase, leukotriene C4, and carboxypeptidase-A3 compared to UN individuals. Following the treatment of Ss infection, each of these granulocyte-associated proteins drops significantly. Our data suggest that eosinophil, neutrophil, and mast cell activation may play a role in the response to Ss infection.

First Responders: Innate Immunity to Helminths

“…NETs have previously been described to facilitate and prolong the exposure of neutrophil intracellular contents such as myeloperoxidase (MPO) to kill bacteria. Likewise, neutrophils and eosinophils were found to require MPO and MBP to kill S. stercoralis larvae in vitro and patients infected with S. stercoralis exhibited elevated serum levels of neutrophil- and eosinophil-derived granular proteins[139, 140], suggesting that NETs may act in a similar manner and extend the exposure of helminths to anti-helminth products secreted by neutrophils, eosinophils and macrophages. Collectively, these studies suggest that neutrophils promote protective immunity to helminths via several effector mechanisms.…”

Trichinella spiralis Calreticulin S-Domain Binds to Human Complement C1q to Interfere With C1q-Mediated Immune Functions

“…ROS and granular proteins (NE, etc.) are directly involved in killing and clearing infections (41,42). In early studies to determine the immune mechanisms involved in the expulsion of T. spiralis infection, the oxidative products and granular proteins released by neutrophils were identified as toxic to NBL (43,44).…”

The Enigma of Eosinophil Degranulation

“…Similarly, no evidence of increased degranulation or morphologic granule difference of circulating eosinophils has been detected in other allergic diseases including asthma, atopic dermatitis, allergic rhinitis and eosinophilic granulomatosis with polyangiitis (EGPA, formerly Churg-Strauss syndrome) compared to healthy individuals [149]. Elevated ECP, EPX, EDN and MBP-1 plasma levels together with an increased AEC have been described in many helminthinfected patients [150]. Additionally, MBP-1, ECP and EPX have been found in association with mtDNA in the formation of EETs [4,45,46,48,151].…”