Cytokine responses of C3H/HeN mice infested with Ixodes scapularis or Ixodes pacificus nymphs

Abstract

Lyme borreliosis, caused by Borrelia burgdorferi, is transmitted by Ixodes scapularis in the eastern and midwestern United States and by Ixodes pacificus in the far-Western United States. Studies have shown that infestation with I. scapularis nymphs modulates host cytokine production; however, the influence of I. pacificus infestation on host cytokines remains uninvestigated. This study demonstrated how repeated infestations with pathogen-free I. scapularis or I. pacificus nymphs affects the production of the macrophage cytokines IL-1beta, IL-6 and tumour necrosis factor-alpha and the T lymphocyte cytokines IL-2, IL-4, IL-5, IL-6, IL-10 and IFN-gamma by C3H/HeN mice. Female mice were infested once or twice with pathogen-free I. scapularis or I. pacificus nymphs, with a 14-day tick-free period between exposures. After each infestation, tick biology parameters were assessed and macrophage and T lymphocyte cytokine production measured by antigen capture ELISA. Acquired resistance to tick feeding did not develop after infestation with either tick species. Differences in cytokine production were observed between infested and noninfested mice, and between mice infested with either I. scapularis or I. pacificus nymphs. Infestations polarized cytokine production towards a Th2 cytokine profile, with suppression of pro-inflammatory Th1 cytokines. This pattern of cytokine production is more pronounced for I. pacificus infested mice.

Langerhans Cell Deficiency ImpairsIxodes scapularisSuppression of Th1 Responses in Mice

“…1 and 2). As expected based on previous studies with BALB/c and C3H/HeN mice (30,42), tick feeding suppressed ConA-induced IFN-␥ production by lymph node (Fig. 1a) and splenic ( Fig.…”

“…I. scapularis tick feeding on mice has been shown to modulate ConA-induced T-cell cytokine production in lymph nodes and spleens, with a reduction in the Th1 cytokine IFN-␥ and an increase in the Th2 cytokine IL-4 (30,42). To determine whether the observed modulation was mediated in part by LCs, we assessed the effects of tick infestation on cytokine responses in WT and Langerin-DTA transgenic mice ( Fig.…”

“…Proteomic analysis of tick saliva has revealed antihemostatic, anti-inflammatory, and immunomodulatory components, which are thought to subdue the host cutaneous immune response and promote ingestion of the blood meal (18,26,34). In addition to effects on local immunity, the feeding of I. scapularis ticks on mice has been reported to result in systemic immune deviation of T-helper (Th) responses toward the anti-inflammatory Th2 type, as assessed by mitogen (concanavalin A) stimulation of lymphocytes harvested from the spleens 7 to 10 days after tick placement (30,(40)(41)(42).…”

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

“…It has been suggested that I. scapularis saliva plays a role in infection, according to experimental model of guinea pig infestation with Borrelia burgdorferi-infected ticks (31). In fact, tick saliva contains molecules that prevent complement activation (32) and T cell proliferation (13,15,33), and that polarize T cell responses to a Th2 profile (34). Tick saliva also modulates cytokine production by epidermal cells (35) and alters expression of adhesion molecules by skin-derived endothelial cells (36).…”

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

“…Development of acquired resistance to tick infestation depends upon the species of tick, host species, and history of prior exposure to tick feeding (Wikel 1996, Brossard andWikel 2004). Laboratory mice infested with I. scapularis or Ixodes pacificus do not develop resistance to repeat infestations (Schoeler et al 2000), while guinea pigs or cattle infested with Dermacentor andersoni develop intense acquired resistance (Allen 1973, Willadsen 1980. Elements of the host immune system implicated in acquired resistance include proinflammatory cytokines, antibodies, T cells, complement, histamine, neutrophils, basophils, and eosinophils (Allen 1973, Theis and Budwiser 1974, Wikel 1996, Brossard and Wikel 2004.…”