Induced Transient Immune Tolerance in Ticks and Vertebrate Host: A Keystone of Tick-Borne Diseases?

Abstract

Ticks and tick transmitted infectious agents are increasing global public health threats due to increasing abundance, expanding geographic ranges of vectors and pathogens, and emerging tick-borne infectious agents. Greater understanding of tick, host, and pathogen interactions will contribute to development of novel tick control and disease prevention strategies. Tick-borne pathogens adapt in multiple ways to very different tick and vertebrate host environments and defenses. Ticks effectively pharmacomodulate by its saliva host innate and adaptive immune defenses. In this review, we examine the idea that successful synergy between tick and tick-borne pathogen results in host immune tolerance that facilitates successful tick infection and feeding, creates a favorable site for pathogen introduction, modulates cutaneous and systemic immune defenses to establish infection, and contributes to successful long-term infection. Tick, host, and pathogen elements examined here include interaction of tick innate immunity and microbiome with tick-borne pathogens; tick modulation of host cutaneous defenses prior to pathogen transmission; how tick and pathogen target vertebrate host defenses that lead to different modes of interaction and host infection status (reservoir, incompetent, resistant, clinically ill); tick saliva bioactive molecules as important factors in determining those pathogens for which the tick is a competent vector; and, the need for translational studies to advance this field of study. Gaps in our understanding of these relationships are identified, that if successfully addressed, can advance the development of strategies to successfully disrupt both tick feeding and pathogen transmission.

Tick host immunity: vector immunomodulation and acquired tick resistance

“…There is a lack of direct experimental evidence addressing the potential for repeated tick infestations in inducing transient immune tolerance in natural or reservoir hosts [131,132]. Studies suggest that T cells collected from BALB/c mice previously infested with I. ricinus exhibit a suppressed response to in vitro concanavalin A stimulation, compared to cells from non-infested mice [133].…”

Resistance to Ticks and the Path to Anti-Tick and Transmission Blocking Vaccines

“…The early observations in bovine acquired resistance and confirmation in laboratory trials and human biopsy studies showed an integral role of histamine and basophils in a successful resistance response against tick infestations. Ticks’ ability to modulate host itch, hemostasis, and immune responses is impressive, redundant, and most evident during an initial infestation for those species that develop and express acquired resistance [ 28 , 48 , 63 , 112 , 113 , 114 , 115 , 116 , 117 ]. Thus, ticks engorge readily, fully, and elicit little cutaneous irritation and inflammation during an initial infestation of species that are capable of developing acquired resistance [ 57 , 118 ].…”

“…Thus, ticks engorge readily, fully, and elicit little cutaneous irritation and inflammation during an initial infestation of species that are capable of developing acquired resistance [ 57 , 118 ]. However, the initial infestation stimulates the development of immune effectors that counteract actions of tick saliva components so that during subsequent infestations the actions of tick modulators of host defenses are diminished and the multiple elements of acquired resistance are expressed [ 28 , 57 , 63 , 107 , 112 , 113 , 114 , 117 , 118 , 119 , 120 , 121 ].…”

“…Two tick-borne encephalitis virus vaccines are licensed in Europe and two vaccines for the Far-Eastern subtype of the virus are licensed in Russia [ 27 ]. Research into such vaccine strategies is showing incremental progress on multiple fronts, and continues to reveal unexpected components and pathways, as well as increasingly complex, dynamic, interconnected relationships that occur at the tick–host–pathogen interface [ 28 ]. These relationships are increasingly being explored in novel ways to develop immunological based tools to control both tick infestations and transmission of tick-borne pathogens of veterinary and human medical importance, including a diverse array of physiologically important molecules of tick tissues and saliva components, as well as organisms such as tick symbionts and the remainder tick microbiome [ 19 , 21 , 22 , 23 , 29 , 30 , 31 , 32 , 33 , 34 ].…”

An Experimental Murine Model to Study Acquisition Dynamics of Tick-Borne Langat Virus in Ixodes Scapularis

“…They have an ability in efficiently taking a blood meal through biting host and allowing viral survival and replication within them for an extensive period of time [20][21][22][23] . Ixodid ticks are reported to be the most prominent vectors that play key role(s) in the flavivirus acquisition and transmission cycle 20 .…”