Dataset Information

Inherited Tolerance in Cattle to the Apicomplexan Protozoan Theileria parva is Associated with Decreased Proliferation of Parasite-Infected Lymphocytes.

ABSTRACT: Theileria parva is the causative agent of East Coast fever and Corridor disease, which are fatal, economically important diseases of cattle in eastern, central and southern Africa. Improved methods of control of the diseases are urgently required. The parasite transforms host lymphocytes, resulting in a rapid, clonal expansion of infected cells. Resistance to the disease has long been reported in cattle from T. parva-endemic areas. We reveal here that first- and second-generation descendants of a single Bos indicus bull survived severe challenge with T. parva, (overall survival rate 57.3% compared to 8.7% for unrelated animals) in a series of five field studies. Tolerant cattle displayed a delayed and less severe parasitosis and febrile response than unrelated animals. The in vitro proliferation of cells from surviving cattle was much reduced compared to those from animals that succumbed to infection. Additionally, some pro-inflammatory cytokines such as IL1β, IL6, TNFα or TGFβ which are usually strongly expressed in susceptible animals and are known to regulate cell growth or motility, remain low in tolerant animals. This correlates with the reduced proliferation and less severe clinical reactions observed in tolerant cattle. The results show for the first time that the inherited tolerance to T. parva is associated with decreased proliferation of infected lymphocytes. The results are discussed in terms of whether the reduced proliferation is the result of a perturbation of the transformation mechanism induced in infected cells or is due to an innate immune response present in the tolerant cattle.

SUBMITTER: Latre de Late P

PROVIDER: S-EPMC8602341 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Inherited Tolerance in Cattle to the Apicomplexan Protozoan Theileria parva is Associated with Decreased Proliferation of Parasite-Infected Lymphocytes.

Latre de Late Perle P Cook Elizabeth A J EAJ Wragg David D Poole E Jane EJ Ndambuki Gideon G Miyunga Antoinette Aluoch AA Chepkwony Maurine C MC Mwaura Stephen S Ndiwa Nicholas N Prettejohn Giles G Sitt Tatjana T Van Aardt Richard R Morrison W Ivan WI Prendergast James G D JGD Toye Philip P

Frontiers in cellular and infection microbiology 20211105

Theileria parva is the causative agent of East Coast fever and Corridor disease, which are fatal, economically important diseases of cattle in eastern, central and southern Africa. Improved methods of control of the diseases are urgently required. The parasite transforms host lymphocytes, resulting in a rapid, clonal expansion of infected cells. Resistance to the disease has long been reported in cattle from T. parva-endemic areas. We reveal here that first- and second-generation d ...[more]

PMID: 34804994

Similar Datasets

Project description:Theileria parva is a protozoan parasite that causes East Coast fever (ECF), an economically important disease of cattle in Africa. It is transmitted mainly by the tick Rhipicephalus appendiculatus. Research efforts to develop a subunit vaccine based on parasite neutralizing antibodies and cytotoxic T-lymphocytes have met with limited success. The molecular mechanisms underlying T. parva life cycle stages in the tick vector and bovine host are poorly understood, thus limiting progress toward an effective and efficient control of ECF. Transcriptomics has been used to identify candidate vaccine antigens or markers associated with virulence and disease pathology. Therefore, characterization of gene expression throughout the parasite's life cycle should shed light on host-pathogen interactions in ECF and identify genes underlying differences in parasite stages as well as potential, novel therapeutic targets. Recently, the first gene expression profiling of T. parva was conducted for the sporoblast, sporozoite, and schizont stages. The sporozoite is infective to cattle, whereas the schizont is the major pathogenic form of the parasite. The schizont can differentiate into piroplasm, which is infective to the tick vector. The present study was designed to extend the T. parva gene expression profiling to the piroplasm stage with reference to the schizont. Pairwise comparison revealed that 3,279 of a possible 4,084 protein coding genes were differentially expressed, with 1,623 (49%) genes upregulated and 1,656 (51%) downregulated in the piroplasm relative to the schizont. In addition, over 200 genes were stage-specific. In general, there were more molecular functions, biological processes, subcellular localizations, and pathways significantly enriched in the piroplasm than in the schizont. Using known antigens as benchmarks, we identified several new potential vaccine antigens, including TP04_0076 and TP04_0640, which were highly immunogenic in naturally T. parva-infected cattle. All the candidate vaccine antigens identified have yet to be investigated for their capacity to induce protective immune response against ECF.

Project description:Many breeds of cattle with long histories of living in areas of endemic disease have evolved mechanisms that enable them to co-exist with specific pathogens. Understanding the genes that control tolerance and resistance could provide new strategies to improve the health and welfare of livestock. Around one sixth of the world cattle population is estimated to be at risk from one of the most debilitating tick-borne diseases of cattle, caused by the protozoan parasite, Theileria annulata. The parasite mainly infects cells of the myeloid lineage which are also the main producers of inflammatory cytokines. If an infectious or inflammatory insult is sufficiently great, inflammatory cytokines produced by macrophages enter the circulation and induce an acute phase proteins (APP) response. The Bos taurus Holstein breed produces higher and more prolonged levels of inflammatory cytokine induced APP than the Bos indicus Sahiwal breed in response to experimental infection with T. annulata. The Sahiwal exhibits significantly less pathology and survives infection, unlike the Holstein breed. Therefore, we hypothesised that the causal genes were likely to be expressed in macrophages and control the production of inflammatory cytokines. A functional genomics approach revealed that the transcriptome profile of the B. taurus macrophages was more associated with an inflammatory programme than the B. indicus macrophages. In particular the most differentially expressed gene was a member of the signal regulatory protein (SIRP) family. These are mainly expressed on myeloid cell surfaces and control inflammatory responses. Other differentially expressed genes included bovine major histocompatibility complex (MHC) (BoLA) class II genes, particularly BoLA DQ, and transforming growth factor (TGF)B2. We are now exploring whether sequence and functional differences in the bovine SIRP family may underlie the resistance or tolerance to T. annulata between the breeds. Potentially, our research may also have more general implications for the control of inflammatory processes against other pathogens. Genes controlling the balance between pathology and protection may determine how livestock can survive in the face of infectious onslaught. Next generation sequencing and RNAi methodologies for livestock species will bring new opportunities to link diversity at the genome level to functional differences in health traits in livestock species.

Project description:BackgroundLittle is known about how apicomplexan parasites have evolved to infect different host species and cell types. Theileria annulata and Theileria parva invade and transform bovine leukocytes but each species favours a different host cell lineage. Parasite-encoded proteins secreted from the intracellular macroschizont stage within the leukocyte represent a critical interface between host and pathogen systems. Genome sequencing has revealed that several Theileria-specific gene families encoding secreted proteins are positively selected at the inter-species level, indicating diversification between the species. We extend this analysis to the intra-species level, focusing on allelic diversity of two major secretome families. These families represent a well-characterised group of genes implicated in control of the host cell phenotype and a gene family of unknown function. To gain further insight into their evolution and function, this study investigates whether representative genes of these two families are diversifying or constrained within the T. annulata population.ResultsStrong evidence is provided that the sub-telomerically encoded SVSP family and the host-nucleus targeted TashAT family have evolved under contrasting pressures within natural T. annulata populations. SVSP genes were found to possess atypical codon usage and be evolving neutrally, with high levels of nucleotide substitutions and multiple indels. No evidence of geographical sub-structuring of allelic sequences was found. In contrast, TashAT family genes, implicated in control of host cell gene expression, are strongly conserved at the protein level and geographically sub-structured allelic sequences were identified among Tunisian and Turkish isolates. Although different copy numbers of DNA binding motifs were identified in alleles of TashAT proteins, motif periodicity was strongly maintained, implying conserved functional activity of these sites.ConclusionsThis analysis provides evidence that two distinct secretome genes families have evolved under contrasting selective pressures. The data supports current hypotheses regarding the biological role of TashAT family proteins in the management of host cell phenotype that may have evolved to allow adaptation of T. annulata to a specific host cell lineage. We provide new evidence of extensive allelic diversity in representative members of the enigmatic SVSP gene family, which supports a putative role for the encoded products in subversion of the host immune response.

Dataset Information

Inherited Tolerance in Cattle to the Apicomplexan Protozoan Theileria parva is Associated with Decreased Proliferation of Parasite-Infected Lymphocytes.

Publications

Inherited Tolerance in Cattle to the Apicomplexan Protozoan <i>Theileria parva</i> is Associated with Decreased Proliferation of Parasite-Infected Lymphocytes.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets