Ixodes scapularis: Effects of Repeated Infestations with Pathogen-Free Nymphs on Macrophage and T Lymphocyte Cytokine Responses of BALB/c and C3H/HeN Mice

Schoeler, George B.; Manweiler, Stephen A.; Wikel, Stephen K.

doi:10.1006/expr.1999.4426

Cited by 80 publications

(81 citation statements)

References 29 publications

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“…It has been shown that the tick saliva or SGE diminish the production of Th1-related cytokines and increase the production of Th2-related cytokines (11)(12)(13)(14). In this study, we have demonstrated that the preferential induction of Th2 responses by tick saliva is also a consequence of its modulatory effect on DCs.…”

Section: Discussionmentioning

confidence: 52%

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Tick Saliva Inhibits Dendritic Cell Migration, Maturation, and Function while Promoting Development of Th2 Responses

Skallová

Iezzi

Ampenberger

et al. 2008

The Journal of Immunology

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Similarly to other blood-feeding arthropods, ticks have evolved immunosuppressive mechanisms enabling them to overcome the host immune system. Although the immunomodulatory effect of tick saliva on several cell populations of the immune system has been extensively studied, little is known about its impact on dendritic cells (DCs). We have examined the effect of Ixodes ricinus tick saliva on DC function in vitro and in vivo. Exposure of DCs to tick saliva in vitro resulted in impaired maturation, upon CD40 or TLR9, TLR3 and TLR7 ligation, as well as reduced Ag presentation capacity. Administration of tick saliva in vivo significantly inhibited maturation and early migration of DCs from inflamed skin to draining lymph nodes, and decreased the capacity of lymph node DCs to present soluble Ag to specific T cells. Moreover, saliva-exposed DCs failed to induce efficient Th1 and Th17 polarization and promoted development of Th2 responses. Our data reveal a complex inhibitory effect exerted by tick saliva on DC function. Given the role of DCs as the key instigators of adaptive immune responses, alteration of their function might represent a major mechanism of tick-mediated immune evasion.

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Section: Discussionmentioning

confidence: 52%

“…Moreover, tick saliva has been reported to favor development of a Th2-type immune response, characterized by production of high levels of IL-4 and IL-10 and low levels of IFN-␥ and IL-12 (11)(12)(13)(14).…”

mentioning

confidence: 99%

Tick Saliva Inhibits Dendritic Cell Migration, Maturation, and Function while Promoting Development of Th2 Responses

Skallová

Iezzi

Ampenberger

et al. 2008

The Journal of Immunology

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“…I. scapularis saliva also reduces the expression of b2-integrin (CD18) that is essential for interactions of human neutrophils with extracellular matrix and decreases the uptake and killing of B. burgdorferi (Montgomery et al 2004). I. scapularis saliva inhibits T-cell proliferation (Urioste et al 1994), contains an interleukin-2 binding protein (Gillespie et al 2001) and polarizes CD4 Tcells to a Th2 cytokine profile (Schoeler et al 1999, Müller-Doblies et al 2007). CD4 ϩ T-cell activation is inhibited by the I. scapularis protein, Salp 15, which binds to extracellular domains of CD4 (Garg et al 2006).…”

Section: Discussionmentioning

confidence: 99%

Dermatologic Changes Induced by RepeatedIxodes scapularisBites and Implications for Prevention of Tick-Borne Infection

Krause

Grant‐Kels

Tahan

et al. 2009

Vector-Borne and Zoonotic Diseases

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Previous studies in rodents and people have demonstrated that repeated tick exposure is associated with reduced Borrelia burgdorferi transmission but the mechanism of prevention remains unclear. We examined the acute histopathologic reactions to initial and repeated Ixodes scapularis bites in BALB/c mice and in people. Skin biopsies of BALB/c mice infested for the first time by I. scapularis nymphs revealed vascular dilatation and an accumulation of inflammatory cells adjacent to the bite site but absent at the site of tick attachment. Such changes would enhance tick-borne pathogen transmission. Mice reexposed to I. scapularis nymphs experienced a decrease in vascular dilatation and a marked increase in inflammatory cells at the site of tick attachment. Skin biopsies of people with attached I. scapularis nymphs revealed similar histologic patterns. These results indicate that cellular changes at the tick-dermal interface following I. scapularis attachment are likely to allow for successful transmission of tick-borne pathogens in non-tick-immune hosts and to inhibit tick-borne pathogen transmission in hosts that have developed tick immunity.

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“…For example, macrophage production of IL-1 and TNF-␣, as well as lymphocyte production of IL-2 and IFN-␥, were diminished in the presence of Dermacentor andersoni salivary gland extracts (16). In addition, splenocytes from C3H/ HeJ mice infested with I. scapularis nymphs presented decreased production of IL-2 and IFN-␥ and increased production of IL-4 and IL-10 when stimulated with Con A (17,18). Also, saliva of Rhipicephalus sanguineus inhibited Con A-induced IL-2 production by splenocytes (19) and IL-12 production by LPS-stimulated bone marrow-derived DCs (20).…”

Section: Endritic Cells (Dcs)mentioning

confidence: 99%

Prostaglandin E2 Is a Major Inhibitor of Dendritic Cell Maturation and Function in Ixodes scapularis Saliva

Sá-Nunes

Báfica

Lucas

et al. 2007

The Journal of Immunology

120

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Tick saliva is thought to contain a number of molecules that prevent host immune and inflammatory responses. In this study, the effects of Ixodes scapularis saliva on cytokine production by bone marrow-derived dendritic cells (DCs) from C57BL/6 mice stimulated by TLR-2, TLR-4, and TLR-9 ligands were studied. Saliva at remarkably diluted concentrations (<1/2000) promotes a dose-dependent inhibition of IL-12 and TNF-α production induced by all TLR ligands used. Using a combination of fractionation techniques (microcon filtration, molecular sieving, and reversed-phase chromatography), we unambiguously identified PGE2 as the salivary inhibitor of IL-12 and TNF-α production by DCs. Moreover, we have found that I. scapularis saliva (dilution 1/200; ∼10 nM PGE2) marginally inhibited LPS-induced CD40, but not CD80, CD86, or MHC class II expression. In addition, saliva significantly suppressed the ability of DCs to stimulate Ag-specific CD4+ T cell proliferation and IL-2 production. Notably, the effect of saliva on DC maturation and function was reproduced by comparable concentrations of standard PGE2. These findings indicate that PGE2 accounts for most inhibition of DC function observed with saliva in vitro. The role of salivary PGE2 in vector-host interaction and host immune modulation and inflammation in vivo is also discussed. This study is the first to identify molecularly a DC inhibitor from blood-sucking arthropods.

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Ixodes scapularis: Effects of Repeated Infestations with Pathogen-Free Nymphs on Macrophage and T Lymphocyte Cytokine Responses of BALB/c and C3H/HeN Mice

Cited by 80 publications

References 29 publications

Tick Saliva Inhibits Dendritic Cell Migration, Maturation, and Function while Promoting Development of Th2 Responses

Tick Saliva Inhibits Dendritic Cell Migration, Maturation, and Function while Promoting Development of Th2 Responses

Dermatologic Changes Induced by RepeatedIxodes scapularisBites and Implications for Prevention of Tick-Borne Infection

Prostaglandin E2 Is a Major Inhibitor of Dendritic Cell Maturation and Function in Ixodes scapularis Saliva

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