The effect of ovine peripheral blood mononuclear cells on <i>Haemonchus contortus</i> larval morbidity in vitro

Shepherd, Elizabeth; Garza, Javier J.; Greiner, Scott Patrick; Bowdridge, Scott A

doi:10.1111/pim.12424

Cited by 4 publications

(7 citation statements)

References 25 publications

(56 reference statements)

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“…Similar responses have been observed in ovine gastrointestinal nematode in vitro models, H. contortus infected STC PBMC (composed of monocytes and lymphocytes) cultured with larvae led to a reduction in larval motility (Holt et al, 2015). Quantifying larval death after culture with PBMC by ATP quantification further found a greater reduction in larval ATP when cultured with STC PBMC than SUF PBMC (Shepherd et al, 2017).…”

Section: Immune Response To Haemonchus Contortussupporting

confidence: 69%

Response of Ovine Neutrophils to Different Life Stages of Haemonchus Contortus

Middleton¹

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Initiation of immune responses to helminth infection require interleukin (IL)-4 receptor signaling, activating signal transducer and activation of transcription 6 (STAT6) and resulting in elevated IL-4 and-13 production. This phenomenon occurs during early Haemonchus contortus (H. contortus) infection in parasite-resistant St. Croix (STC) sheep, yet the cell responsible for early cytokine production is unknown. Studies have reported greater infiltration of neutrophils to the abomasum of STC by 3 days after H. contortus infection as compared to parasite-susceptible Suffolk sheep (SUF). Neutrophils have been noted to play a role in immune responses to murine helminth infections through production of IL-13, which promotes alternative macrophage polarization. Thus, it is reasonable to hypothesize that neutrophils are an early source of IL-4/IL-13 that promote resistance to H. contortus infection. This study aimed to determine differences in ovine neutrophil responses when stimulated with antigen (Ag) from larval and adult stages of H. contortus. Neutrophils from STC and SUF sheep were cultured with either larval (HcLA) or adult (HcWA) antigen. In vitro production of (IL-4/IL-13) cytokine were measured using an ovine-specific enzyme-linked immunosorbent assay (ELISA). Neutrophils from either breed exposed to HcLA produced significantly higher levels of IL-4 by 30 minutes (STC, 3153.65 pg/ml and SUF, 4665.22 pg/ml) and IL-13 by 6 hours (STC, 391.02 pg/ml and SUF, 419.6 pg/ml) when compared to neutrophils cultured with HcWA (STC IL-4, 6.04 pg/ml and SUF, 8.05 pg/ml, respectively) (STC IL-13, 10 pg/ml and 12.5 pg/ml) (P < 0.001). While no breed differences were observed, these data indicate that neutrophils preferentially respond to HcLA compared to HcWA. Taken together these data indicate that neutrophils are a potential effector cell responsible for initiating early Th2 responses during H. contortus infection in sheep.

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Section: Immune Response To Haemonchus Contortussupporting

confidence: 69%

Response of Ovine Neutrophils to Different Life Stages of Haemonchus Contortus

Middleton¹

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“…There were no differences in ATP levels of L3 exposed to challenged Suffolk neutrophils compared to live controls. While the ATP levels of primed St. Croix neutrophil‐exposed larvae were higher than heat‐killed larvae, ATP levels were below the threshold for larval morbidity previously established (Figure C).…”

Section: Resultsmentioning

confidence: 56%

“…Our laboratory has previously shown that ovine peripheral blood mononuclear cells impair L3 motility quantified by decreases in both movement and ATP levels in vitro . We next sought to evaluate the ability of larval‐bound neutrophils to similarly impair their targets by measuring larval ATP after exposure to challenged St. Croix and Suffolk‐derived cells.…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies have highlighted a role of cellular and innate immune components in trapping and killing of Hc larvae in vitro. Shepherd et al . recently identified a role for killing of third‐stage larvae (L3) by bound St. Croix peripheral blood mononuclear cells (PBMC) that occurs at a higher magnitude compared to Suffolk‐derived cells.…”

Section: Introductionmentioning

confidence: 99%

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Ovine vital neutrophil extracellular traps bind and impair Haemonchus contortus L3 in a breed‐dependent manner

Garza

Greiner

Bowdridge

2018

Parasite Immunology

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This study aimed to characterize neutrophil response to Haemonchus contortus (Hc) in vitro using cells from parasite-resistant St. Croix (STC) and parasite-susceptible Suffolk (SUF) sheep. Neutrophils from Hc-primed and naive STC and SUF sheep were incubated with Hc larval antigen (HcLA), Hc worm antigen (HcWA) or complete media (CM). After HcLA exposure, neutrophils from STC and SUF formed extracellular traps composed of DNA. Stimulation with HcLA induced a 35-fold increase in extracellular DNA compared to CM controls. However, extracellular DNA was not found when neutrophils were cultured with HcWA. The formation of neutrophil extracellular traps (NET) in response to HcLA yields a low percentage of necrotic cells indicating a form of vital NETosis. Neutrophils from primed and naïve STC bound Hc L3 greater (93% and 68%) than SUF (78% and 45%; P < 0.001). Furthermore, STC neutrophils significantly reduced larval ATP levels compared to SUF neutrophils (0.05 μmol/L vs 0.1 μmol/L ATP, P < 0.001). These data indicate that ovine neutrophils bind, form vital NET and reduce ATP to Hc L3 in a breed and infection status-dependent manner.

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“…Our previous data have indicated that ovine PBMC can severely inhibit Hc larval motility and increase larval morbidity 17,18 . Therefore, the objective of this study was to determine which cell subset of PBMC contributes to larval morbidity using ATP quantification.…”

Section: Introductionmentioning

confidence: 99%

Characterization of ovine monocyte activity when cultured with Haemonchus contortus larvae in vitro

Shepherd

Greiner

Bowdridge

2020

Parasite Immunology

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Helminth infection generally elicits a T-helper 2 (Th2) type response, producing key cytokines such as IL-4 and IL-13, which influence downstream effector function, shape immunopathology and ultimately confer protection against disease. 1 However, different breeds of sheep display different levels of resistance to haematophagous gastrointestinal nematode, Haemonchus contortus (Hc). St. Croix (STC) hair sheep have been reported to have 99% fewer worms recovered from the abomasum when compared to parasite-susceptible sheep 2,3 and are considered naturally resistant to Hc. Breeds of sheep displaying higher levels of resistance to Hc express genes associated with Th2 responses in cells recovered from abomasal lymph nodes, 4-6 and thus, immune-mediated resistance suggests breeds of sheep that naturally expel Hc are reliant on a greater cellular immune response. 3,7 Peripheral blood mononuclear cells (PBMCs) are a heterogeneous population of cells comprised of lymphocytes and monocytes. Lymphocytes are important in generating immune responses against helminths, primarily through induction of CD4 + Th2 cells, along with

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The effect of ovine peripheral blood mononuclear cells on Haemonchus contortus larval morbidity in vitro

Cited by 4 publications

References 25 publications

Response of Ovine Neutrophils to Different Life Stages of Haemonchus Contortus

Response of Ovine Neutrophils to Different Life Stages of Haemonchus Contortus

Ovine vital neutrophil extracellular traps bind and impair Haemonchus contortus L3 in a breed‐dependent manner

Characterization of ovine monocyte activity when cultured with Haemonchus contortus larvae in vitro

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