Apoptosis and Autophagy: Current Understanding in Tick-Pathogen Interactions.

Xin-Ru Wang,Benjamin Cull

doi:10.3389/fcimb.2022.784430

Xin-Ru Wang, Benjamin Cull

Open Access

https://doi.org/10.3389/fcimb.2022.784430

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Abstract

Tick-borne diseases are a significant threat to human and animal health throughout the world. How tick-borne pathogens successfully infect and disseminate in both their vertebrate and invertebrate hosts is only partially understood. Pathogens have evolved several mechanisms to combat host defense systems, and to avoid and modulate host immunity during infection, therefore benefitting their survival and replication. In the host, pathogens trigger responses from innate and adaptive immune systems that recognize and eliminate invaders. Two important innate defenses against pathogens are the programmed cell death pathways of apoptosis and autophagy. This Mini Review surveys the current knowledge of apoptosis and autophagy pathways in tick-pathogen interactions, as well as the strategies evolved by pathogens for their benefit. We then assess the limitations to studying both pathways and discuss their participation in the network of the tick immune system, before highlighting future perspectives in this field. The knowledge gained would significantly enhance our understanding of the defense responses in vector ticks that regulate pathogen infection and burden, and form the foundation for future research to identify novel approaches to the control of tick-borne diseases.

Highlights

Ticks, as obligate blood-sucking arthropods, can cause substantial public health burdens by direct feeding behaviors and transmitting a broad range of viral, bacterial, and protozoan pathogens to hosts
Characterization of the involvement of the tick PCD machinery in pathogen acquisition, persistence, and transmission would help explain the natural cycle of tick-borne pathogens, as well as lead to the design of specific targets for new vaccines and drugs to prevent or treat tick-borne diseases (TBDs)
Greater knowledge of tick-borne intracellular pathogen and host interplay could have implications for understanding how the innate immune system contributes to the vector competence of various tick species for different intracellular pathogens and to the ability of vertebrate hosts to act as reservoirs or succumb to disease

Summary

INTRODUCTION

As obligate blood-sucking arthropods, can cause substantial public health burdens by direct feeding behaviors and transmitting a broad range of viral, bacterial, and protozoan pathogens to hosts. Tick-borne obligate intracellular pathogens include arboviruses and bacteria, which are responsible for diseases of medical and veterinary importance globally These pathogens use different strategies to survive within their hosts. A similar but distinct process to induce autophagy and trafficking of autophagosomes to the pathogen-containing vacuole is employed by Ehrlichia chaffeensis (causative agent of human ehrlichiosis) via its effector Etf-1, which interacts with Rab, Beclin and the autophagyinitiating class III phosphatidylinositol 3-kinase complex (Lin et al, 2016) Both A. phagocytophilum and E. chaffeensis prevent their vacuoles fusing with the lysosome (Niu et al, 2008; Lin et al, 2016; Lina et al, 2017); this is achieved by E. chaffeensis through modulation of the Wnt signaling pathway to inhibit autolysosome formation (Lina et al, 2017). We can use the situation in vertebrates as a basis for predicting what might occur in ticks, we cannot assume that the strategies employed by pathogens to infect mammals can be generalized to their persistence in arthropods (as shown above with apoptosis), and so further investigation into how pathogens interact with tick autophagy are warranted

DISCUSSION

SUMMARY