Identification of Theileria lestoquardi Antigens Recognized by CD8+ T Cells

Goh, Shan; Ngugi, Daniel; Lizundia, Regina; Hostettler, Isabel C.; Woods, Kerry; Ballingall, Keith T.; MacHugh, Niall D.; Morrison, W. Ivan; Weir, William; Shiels, Brian; Werling, Dirk

doi:10.1371/journal.pone.0162571

Cited by 12 publications

(20 citation statements)

References 41 publications

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“…A low degree of serological cross-immune reactivity has been detected between T. ovis and T. lestoquardi together with the relatively long duration of a detectable antibody response 17 , but it is unclear whether this provides cross protection against disease. There is evidence that immunity to T. lestoquardi in sheep involves T cell mediated responses 18 against the macroschizont infected leukocyte and similar immune responses have been reported for T. annulata and T. parva 19 . Genetic and antigenic similarities are evident for T. lestoquardi and T. annulata, and cross-immunity between the two species has been demonstrated 17,20 .…”

Section: Discussionsupporting

confidence: 64%

Dynamics and within-host interaction of Theileria lestoquardi and T. ovis among naive sheep in Oman

Awad

Gadalla

Postigo

et al. 2020

Sci Rep

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Mixed species infections of Theileria spp. are common in nature. Experimental and epidemiological data suggest that mixed species infections elicit cross-immunity that can modulate pathogenicity and disease burden at the population level. The present study examined within-host interactions, over a period of 13 months during natural infections with two Theileria spp., pathogenic (T. lestoquardi) and non-pathogenic (T. ovis), amongst a cohort of naive sheep in Oman. In the first two months after exposure to infection, a high rate of mortality was seen among sheep infected with T. lestoquardi alone. However, subsequently mixed-infections of T. lestoquardi and T. ovis prevailed, and no further death occurred. The overall densities of both parasite species were significantly higher as single infection vs mixed infection and the higher relative density of pathogenic T. lestoquardi indicated a competitive advantage over T. ovis in mixed infection. The density of both species fluctuated significantly over time, with no difference in density between the very hot (May to August) and warm season (September to April). A high degree of genotype multiplicity was seen among T. lestoquardi infections, which increased with rising parasite density. Our results illustrate a potential competitive interaction between the two ovine Theileria spp., and a substantial reduction in the risk of mortality in mixed parasite infections, indicating that T. ovis confers heterologous protection against lethal T. lestoquardi infection.

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Section: Discussionsupporting

confidence: 64%

Dynamics and within-host interaction of Theileria lestoquardi and T. ovis among naive sheep in Oman

Awad

Gadalla

Postigo

et al. 2020

Sci Rep

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“…The present study represents the first broad population genetic analysis of T. lestoquardi in Sudan using seven micro-and mini-satellite markers of T. annulata (Weir et al, 2007). Biological and molecular phylogenetic studies clearly indicated that T. lestoquardi is more closely related to T. annulata than to T. parva Schnittger et al, 2003, Goh et al, 2016. Both species were probably evolved from a common ancestor and this fact is supported biologically such as both parasites share the same vector tick.…”

Section: Discussionsupporting

confidence: 58%

Genotyping of Theileria lestoquardi from sheep and goats in Sudan to support control of Malignant Ovine Theileriosis

Ali

Salih

Njahira

et al. 2017

Veterinary Parasitology

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Theileriosis, caused by parasitic protozoa of the genus Theileria parasites, are among the major tick-borne diseases of ruminant livestock. The largest economic losses are attributed in particular to those caused by the leukoproliferative species of Theileria: T. parva, T. annulata and T. lestoquardi. Theileria lestoquardi is transmitted by Hyalomma ticks and causes malignant ovine theileriosis (MOT), a disease that is particularly prevalent in Sudan. The disease is considered of a high economic importance in Sudan, where export of sheep is a major component of the national economy. A live vaccine based on a Sudanese isolate of T. lestoquardi (Atbara strain) was previously developed for the control of MOT in Sudan, but not yet deployed in the field. The present study aims to genetically characterize and compare samples of T. lestoquardi circulating in Sudan as well as the live vaccine isolate in order to understand vaccine breakthroughs and failure that may occur. Sheep and goats blood samples were collected from six regions in Sudan that are known to be endemic for T. lestoquardi infection or have experienced outbreaks of MOT. Blood samples infected with T. lestoquardi were identified by PCR or RLB. Genotyping was carried out by (1) sequencing the homologues of two T. parva CD8 T cell antigen genes, Tp1 and Tp2, and (2) using a panel of seven micro- and mini-satellite markers. A total of 100 T. lestoquardi positive field samples and the T. lestoquardi (Atbara) vaccine were genotyped. The results showed that all samples had mixed genotypes, with several alleles identified at one or more loci. The gene diversity ranged from 0.7840 (TS8) to 0.2133 (TS12) with mean values of 0.5470. PCA revealed three clusters of the parasite in Sudan; interestingly one independent cluster was clearly seen, corresponding to the vaccine isolate. The T. lestoquardi Tp1 homologue showed higher homology with T. annulata than with T. parva sequences included the defined single CD8 T cell target epitope region. The result indicates that multiple genotypes are a common feature of T. lestoquardi infection in Sudan. Both genotyping and the sequencing results clearly showed that the vaccine isolate is highly distinct from the field samples. This finding raised the question whether vaccination with the prepared lived vaccine will effectively protect animals against challenges by the field isolates of T. lestoquardi. The results of this work will inform on the best approach for controlling MOT in Sudan.

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“…AH-1 cells were re-suspended to a concentration of 1 × 10 5 ml in PBS supplemented with 0.05 % (w/v) NaN 3 (Sigma-Aldrich), 5% ΔHFBS (flow buffer), and stained for viable cells using the Live/Dead® Fixable Violet Dead Cell Stain (Invitrogen, Thermo Fisher Scientific) prior to labeling with the ovine MHC class I specific monoclonal antibody (mAb) IL-A88 at a 1:2 dilution of hybridoma tissue culture supernatant (14). This antibody has previously been shown to bind surface expressed recombinant ovine MHC class I on transfected COS-7 cells (15).…”

Section: Methodsmentioning

confidence: 99%

Immunological Homeostasis at the Ovine Placenta May Reflect the Degree of Maternal Fetal Interaction

et al. 2019

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Successful mammalian pregnancies are a result of complex physiological, endocrinological, and immunological processes that combine to create an environment where the mother is tolerant to the semi-allogeneic fetus. Our knowledge of the mechanisms that contribute to maternal tolerance is derived mainly from human and murine studies of haemochorial placentation. However, as this is the most invasive type of placentation it cannot be assumed that identical mechanisms apply to the less invasive epitheliochorial placentation found in other species such as ruminants. Here, we examine three features associated with reproductive immune regulation in a transformed ovine trophoblast cell line and ex-vivo ovine reproductive tissues collected at term, namely: major histocompatibility complex (MHC) expression, Indoleamine 2,3 dioxygenase-1 (IDO-1) expression, and Natural Killer (NK) cell infiltration. High levels of MHC class I protein expression were detected at the surface of the trophoblast cell line using a pan-MHC class I specific monoclonal antibody. The majority of MHC class I transcripts isolated from the cell line clustered with classical MHC alleles. Transcriptional analysis of placental tissues identified only classical MHC class I transcripts. We found no evidence of constitutive transcription of IDO-1 in either the trophoblast cell line or placental tissues. Ex-vivo tissues collected from the materno-fetal interface were negative for cells expressing NKp46/NCR1. Collectively, these observations suggest that the relatively non-invasive synepitheliochorial placentation found in sheep has a more limited requirement for local immunoregulation compared to the more invasive haemochorial placentation of primates and rodents.

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Identification of Theileria lestoquardi Antigens Recognized by CD8+ T Cells

Cited by 12 publications

References 41 publications

Dynamics and within-host interaction of Theileria lestoquardi and T. ovis among naive sheep in Oman

Dynamics and within-host interaction of Theileria lestoquardi and T. ovis among naive sheep in Oman

Genotyping of Theileria lestoquardi from sheep and goats in Sudan to support control of Malignant Ovine Theileriosis

Immunological Homeostasis at the Ovine Placenta May Reflect the Degree of Maternal Fetal Interaction

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