Innate Immune Response to Tick-Borne Pathogens: Cellular and Molecular Mechanisms Induced in the Hosts

Abstract

Many pathogens are transmitted by tick bites, including Anaplasma spp., Ehrlichia spp., Rickettsia spp., Babesia and Theileria sensu stricto species. These pathogens cause infectious diseases both in animals and humans. Different types of immune effector mechanisms could be induced in hosts by these microorganisms, triggered either directly by pathogen-derived antigens or indirectly by molecules released by host cells binding to these antigens. The components of innate immunity, such as natural killer cells, complement proteins, macrophages, dendritic cells and tumor necrosis factor alpha, cause a rapid and intense protection for the acute phase of infectious diseases. Moreover, the onset of a pro-inflammatory state occurs upon the activation of the inflammasome, a protein scaffold with a key-role in host defense mechanism, regulating the action of caspase-1 and the maturation of interleukin-1β and IL-18 into bioactive molecules. During the infection caused by different microbial agents, very similar profiles of the human innate immune response are observed including secretion of IL-1α, IL-8, and IFN-α, and suppression of superoxide dismutase, IL-1Ra and IL-17A release. Innate immunity is activated immediately after the infection and inflammasome-mediated changes in the pro-inflammatory cytokines at systemic and intracellular levels can be detected as early as on days 2–5 after tick bite. The ongoing research field of “inflammasome biology” focuses on the interactions among molecules and cells of innate immune response that could be responsible for triggering a protective adaptive immunity. The knowledge of the innate immunity mechanisms, as well as the new targets of investigation arising by bioinformatics analysis, could lead to the development of new methods of emergency diagnosis and prevention of tick-borne infections.

Galectin-3 in Cardiovascular Diseases

“…In the acute inflammatory response, Gal-3 acts as a promoter of chemoattraction of monocytes/ macrophages [30], neutrophil clearance [31], opsonization of apoptotic neutrophils [32], and mast cell degranulation [33]. Moreover, in macrophages and epithelial cells, Gal-3 binds galactoside-associated membrane remnants from vacuoles produced by some intravacuolar bacteria to actively evade the phagolysosomal pathway of the host [34][35][36]. This binding allows to target damaged vesicles for autophagy through the recruitment of autophagy adaptor proteins.…”

Natural Killer Cells in Immunotherapy: Are We Nearly There?

“…A variety of emerging bacterial infectious diseases are transmitted through ticks, and include pathogenic species such as Anaplasma spp., Ehrlichia spp., and Rickettsia spp. (reviewed in [114]). In detail, Anaplasma phagocytophilum infection, which causes human granulocytic anaplasmosis, induces a proinflammatory disease state with innate immune cell activation.…”

Immune Response to Tick-Borne Hemoparasites: Host Adaptive Immune Response Mechanisms as Potential Targets for Therapies and Vaccines

“…The protective effects on infectious diseases by different branches of immunity are related to the phases of the infection. Effector mechanisms of innate immune responses, rapidly displayed by the host, are able to inhibit the symptoms of the acute phase of infections [ 143 ], while the T- and B cell responses, mounted by the immune system after a while, are able to induce a long-term protection against pathologies induced by hemoparasites. Many different molecules are able to induce T- and/or B cell responses and could be considered as candidate vaccine antigens ( Table 1 ).…”