Submitted to: Parasites & Vectors
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/5/2010
Publication Date: 11/5/2010
Citation: Brake, D.K., Tidwell, J.P., Wikel, S.K., Perez De Leon, A.A. 2010. Rhipicephalus microplus salivary gland molecules induce differential CD86 expression in murine macrophages. Parasites and Vectors. 3(1):Article 103.
Interpretive Summary: The National Cattle Fever Tick Eradication Program (CFTEP) succeeded in eradicating cattle fever ticks (CFT) from the United States in 1943. CFT remain endemic in Mexico where they transmit pathogens that cause cattle fever. Evolving resistance to acaricides among CFT populations in Mexico represents a threat to the U.S. livestock industry. Ticks have a complex repertoire of molecules to modulate host immune responses to facilitate blood feeding. Understanding tick-host interactions presents an opportunity to enhance immunologically-based approaches to eliminate CFT, like the use of anti-tick vaccines. Antigen presenting cells (APCs), play a critical role in activating immune responses elicited in cattle by CFT feeding. We hypothesized that CFT molecules can modulate the expression of co-stimulatory molecules on the surface of APCs thereby altering host defense mechanisms. Our results indicate salivary gland extract (SGE) obtained from the southern cattle tick, Rhipicephalus (Boophilus) microplus, alters the expression of murine CD86, an important co-stimulatory molecule of APCs. These observations could have implications on the ability of CFT to transmit disease-causing agents to cattle. Similar to observations in other ticks species, our findings indicate that bioactive factors in the salivary glands of R. microplus modulate key immune processes that occur early in the development of defense responses mounted by the host against tick feeding. These studies support research by our group toward the identification of new tick molecules that can be tested as antigens to develop the next generation of vaccines with enhanced efficacy against R. microplus.
Technical Abstract: Tick parasitism is a major impediment for cattle production in many parts of the world. The southern cattle tick, Rhipicephalus (Boophilus) microplus, is an obligate hematophagous parasite of domestic and wild animals that serves as vector of infectious agents lethal to cattle. Novel control strategies are required to keep the U.S. free of CFT in a sustainable manner. Tick saliva contains molecules evolved to modulate host innate and adaptive immune responses which facilitates blood feeding and pathogen transmission. Tick feeding promotes CD4 T cell polarization to a Th2 profile, which is usually accompanied by down-regulation of Th1 cytokines through as yet undefined mechanisms. Co-stimulatory molecules on antigen presenting cells are central to T cell processes including the development of Th1 and Th2 responses. Tick induced changes to antigen presenting cell signal transduction pathways are largely unknown. We examined changes in co-stimulatory molecule expression in murine RAW 264.7 cells in response to R. microplus SGE exposure in the presence of the TLR4 ligand, LPS. After 24 hours, CD86, but not CD80, was preferentially up-regulated on mouse macrophage RAW 264.7 cells when treated with LPS and SGE, but not SGE alone. CD80 and CD40 expression was increased with LPS, but the addition of SGE did not alter expression. Higher concentrations of SGE were less effective at increasing CD86 mRNA expression. The addition of mitogen, or extracellular kinase (MEK) inhibitor, PD98059, significantly reduced the ability for SGE to induce CD86 expression, indicating activation of MEK is necessary for SGE induced up-regulation. In conclusion, molecules in R. microplus SGE have a concentration-dependent effect on differential up-regulation of CD86 in macrophages activated by the TLR4-ligand, LPS. Up-regulation of CD86 is at least partially dependent on the MEK pathway, which may drive host T cell responses towards a Th2 phenotype. Identifying tick immunomodulation mechanisms offers the opportunity to enhance immunologically-based approaches to eliminate CFT, like the use of anti-tick vaccines.