Mast cells and basophils are potent effector cells of the innate immune system, and they have both beneficial and detrimental functions for the host. They are mainly implicated in pro-inflammatory responses to allergens but can also contribute to protection against pathogens. Although both cell types were identified more than 130 years ago by Paul Ehrlich, their in vivo functions remain poorly understood. The precursor cell populations that give rise to mast cells and basophils have recently been characterized and isolated. Furthermore, new genetically modified mouse strains have been developed, which enable more specific targeting of mast cells and basophils. Such advances offer new opportunities to uncover the true in vivo activities of these cells and to revisit their previously proposed effector functions.

Protective and pathological roles of mast cells and basophils

The tick-borne intracellular pathogen Anaplasma marginale (Rickettsiales: Anaplasmataceae) develops persistent infections in cattle and tick hosts While erythrocytes appear to be the only site of infection in cattle, A marginale undergoes a complex developmental cycle in ticks and transmission occurs via salivary glands during feeding Many geographic isolates occur that vary in genotype, antigenic composition, morphology and infectivity for ticks In this chapter we review recent research on the host-vector-pathogen interactions of A marginale Major surface proteins (MSPs) play a crucial role in the interaction of A marginale with host cells The MSP1a protein, which is an adhesin for bovine erythrocytes and tick cells, is differentially regulated and affects infection and transmission of A marginale by Dermacentor spp ticks MSP2 undergoes antigenic variation and selection in cattle and ticks, and contributes to the maintenance of persistent infections Phylogenetic studies of A marginale geographic isolates using msp4 and msp1alpha provide information about the biogeography and evolution of A marginale: msp1alpha genotypes evolve under positive selection pressure Isolates of A marginale are maintained by independent transmission events and a mechanism of infection exclusion in cattle and ticks allows for only the infection of one isolate per animal Prospects for development of control strategies by use of pathogen and tick-derived antigens are discussed The A marginale/vector/host studies described herein could serve as a model for research on other tick-borne rickettsiae

Anaplasma marginale (Rickettsiales: Anaplasmataceae): recent advances in defining host-pathogen adaptations of a tick-borne rickettsia.

Tick modulation of host immunity: an important factor in pathogen transmission.

Ticks are ectoparasitic arthropods that can transmit a variety of microorganisms to humans and animals during blood feeding, causing serious infectious disorders, including Lyme disease. Acaricides are pharmacologic agents that kill ticks. The emergence of acaricide-resistant ticks calls for alternative control strategies for ticks and tick-borne diseases. Many animals develop resistance to ticks after repeated infestations, but the nature of this acquired anti-tick immunity remains poorly understood. Here we investigated the cellular and molecular mechanisms underlying acquired resistance to Haemaphysalis longicornis ticks in mice and found that antibodies were required, as was IgFc receptor expression on basophils but not on mast cells. The infiltration of basophils at tick-feeding sites occurred during the second, but not the first, tick infestation. To assess the requirement for basophil infiltration to acquired tick resistance, mice expressing the human diphtheria toxin receptor under the control of the mast cell protease 8 (Mcpt8) promoter were generated. Diphtheria toxin administration to these mice selectively ablated basophils. Diphtheria toxin-mediated basophil depletion before the second tick infestation resulted in loss of acquired tick resistance. These data provide the first clear evidence, to our knowledge, that basophils play an essential and nonredundant role in antibody-mediated acquired immunity against ticks, which may suggest new strategies for controlling tick-borne diseases.

/pdf/selective-ablation-of-basophils-in-mice-reveals-their-59r372jihi.pdf

Selective ablation of basophils in mice reveals their nonredundant role in acquired immunity against ticks

Ticks require blood meal to complete development and reproduction. Multifunctional tick salivary glands play a pivotal role in tick feeding and transmission of pathogens. Tick salivary molecules injected into the host modulate host defence responses to the benefit of the feeding ticks. To colonize tick organs, tick-borne microorganisms must overcome several barriers, i.e., tick gut membrane, tick immunity, and moulting. Tick-borne pathogens co-evolved with their vectors and hosts and developed molecular adaptations to avoid adverse effects of tick and host defences. Large gaps exist in the knowledge of survival strategies of tick-borne microorganisms and on the molecular mechanisms of tick-host-pathogen interactions. Prior to transmission to a host, the microorganisms penetrate and multiply in tick salivary glands. As soon as the tick is attached to a host, gene expression and production of salivary molecules is upregulated, primarily to facilitate feeding and avoid tick rejection by the host. Pathogens exploit tick salivary molecules for their survival and multiplication in the vector and transmission to and establishment in the hosts. Promotion of pathogen transmission by bioactive molecules in tick saliva was described as saliva-assisted transmission (SAT). SAT candidates comprise compounds with anti-haemostatic, anti-inflammatory and immunomodulatory functions, but the molecular mechanisms by which they mediate pathogen transmission are largely unknown. To date only a few tick salivary molecules associated with specific pathogen transmission have been identified and their functions partially elucidated. Advanced molecular techniques are applied in studying tick-host-pathogen interactions and provide information on expression of vector and pathogen genes during pathogen acquisition, establishment and transmission. Understanding the molecular events on the tick-host-pathogen interface may lead to development of new strategies to control tick-borne diseases.

/pdf/tick-salivary-compounds-their-role-in-modulation-of-host-5a0xm8u8il.pdf

Tick salivary compounds: their role in modulation of host defences and pathogen transmission.

Female BALB/c mice were infested four times with pathogen-free Ixodes scapularis nymphs prior to infestation with nymphs infected with Borrelia burgdorferi B31. Each infestation was separated by a 14-day tick-free period. Mean weights of fed ticks and percentage reaching repletion did not indicate development of acquired resistance. Only 16.7% of mice repeatedly infested with pathogen-free ticks prior to infected I. scapularis nymph challenge became positive for B. burgdorferi. One hundred percent of control mice infested only with infected ticks were culture positive for B. burgdorferi.

J Piesman

Papers

Infestation with pathogen-free nymphs of the tick Ixodes scapularis induces host resistance to transmission of Borrelia burgdorferi by ticks.