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

Perle Latre De Late,Stephen Mwaura,Elizabeth A J Cook,Antoinette Aluoch Miyunga,E Jane Poole,Giles Prettejohn,Gideon Ndambuki,Tatjana Sitt,Richard Van Aardt,David Wragg,W Ivan Morrison,Maurine C Chepkwony,Philip Toye,James G D Prendergast,Nicholas Ndiwa

doi:10.3389/fcimb.2021.751671

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.

Highlights

Theileria parva is a tick-transmitted, apicomplexan parasite whose natural host is the African buffalo (Syncerus caffer), in which it causes few clinical signs
The results show that the surviving animals underwent a delayed and less intense parasitosis and febrile episode compared to the unrelated animals that succumbed to the field challenge
The initial indication of tolerance among the related Boran animals was detected in a vaccine study undertaken in 2013 (Sitt et al, 2015), in which animals were exposed to a natural field challenge in an area of buffalo-derived T. parva challenge

Summary

Introduction

Theileria parva is a tick-transmitted, apicomplexan parasite whose natural host is the African buffalo (Syncerus caffer), in which it causes few clinical signs. A clinically distinguishable form of disease called Corridor disease occurs in cattle when the parasite is transmitted directly from buffalo through ticks to cattle, as opposed to the cattle-tick-cattle transmission responsible for ECF. The only currently available interventions to prevent ECF are intensive acaricide treatment to reduce tick infestation, and administration of a live sporozoite vaccine called ITM, the Infection and Treatment Method (Di Giulio et al, 2009). Both of these methods have major drawbacks. There is an urgent need for new control methods to combat ECF

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Results

Conclusion