Third-stage Gnathostoma spinigerum larva excretory secretory antigens modulate function of Fc gamma receptor I-mediated monocytes in peripheral blood mononuclear cell culture

Surachet Benjathummarak; Ratchanok Kumsiri; Supaporn Nuamtanong; Thareerat Kalambaheti; Jitra Waikagul; Nareerat Viseshakul; Yaowapa Maneerat

doi:10.1186/s41182-016-0005-x

Third-stage Gnathostoma spinigerum larva excretory secretory antigens modulate function of Fc gamma receptor I-mediated monocytes in peripheral blood mononuclear cell culture

Trop Med Health. 2016 Apr 21:44:5. doi: 10.1186/s41182-016-0005-x. eCollection 2016.

Authors

Surachet Benjathummarak¹, Ratchanok Kumsiri², Supaporn Nuamtanong³, Thareerat Kalambaheti⁴, Jitra Waikagul³, Nareerat Viseshakul⁵, Yaowapa Maneerat⁶

Affiliations

¹ Center of Excellence for Antibody Research, Faculty of Tropical Medicine, Mahidol University, 10400 Bangkok, Thailand.
² Pathobiology Unit, Department of Medical Science, Faculty of Science, Rangsit University, Pathumthani, 12000 Thailand.
³ Department of Helminthology, Faculty of Tropical Medicine, Mahidol University, Bangkok, 10400 Thailand.
⁴ Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Bangkok, 10400 Thailand.
⁵ Parasitology Unit, Department of Pathology, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, 10330 Thailand.
⁶ Department of Tropical Pathology, Faculty of Tropical Medicine, Mahidol University, Bangkok, 10400 Thailand.

Abstract

Background: Third (infective)-stage Gnathostoma spinigerum larvae (L3) mainly cause human gnathostomiasis. G. spinigerum L3 migrate throughout the subcutaneous tissues, vital organs, and central nervous system and can cause various pathogenesis including sudden death. Interestingly, G. spinigerum L3 can survive and evade host cellular immunity for months or years. The effects of G. spinigerum excretory-secretory (ES) products involved in larval migration and immune-evasive strategies are unknown. Monocytes are innate immune cells that act as phagocytic and antigen-presenting cells and also play roles against helminthic infections via a complex interplay between other immune cells. Fc gamma receptor I (FcγRI) is a high-affinity receptor that is particularly expressed on monocytes, macrophages, and dendritic cells. The cross-linking of FcγRI and antigen-antibody complex initiates signal transduction cascades in phagocytosis, cytokine production, and antibody-dependent cell-mediated cytotoxicity (ADCC). This study investigated whether ES antigen (ESA) from G. spinigerum L3 affects monocyte functions.

Results: Cultures of normal peripheral blood mononuclear cells (PBMC) separated from healthy buffy coats were used as a human immune cell model. ESA was prepared from G. spinigerum L3 culture. Using Real-Time quantitative reverse transcription-polymerase chain reaction (qRT-PCR), the effect of ESA to down-regulate FcγRI mRNA expression in monocytes during 90 min of observation was not well delineated. Flow cytometry analysis revealed a significant phenotypic-decreased FcγRI expression on the monocyte surface at 12 hours (h) of cultivation with the ESA (p = 0.033). Significantly reduced monocyte-mediated phagocytosis capacity was consistently observed after 12 h of ESA pretreatment (p = 0.001).

Conclusions: Our results suggest that G. spinigerum ESA modulates monocyte function via depletion of FcγRI expression. This study provides preliminary information for future in-depth studies to elucidate mechanisms of the immune-evasive strategy of G. spinigerum larvae.

Keywords: Excretory-secretory; FcγRI; Gnathostoma spinigerum; Monocytes; Phagocytosis.