Determinants of memory in experimental filarial infections in mice.

In this communication, we examine the determinants and duration of memory responses against filarial parasites using an intraperitoneal mouse model of Brugia pahangi infection. We assessed the role of T cells in the memory response against B. pahangi larvae by transferring splenic T cells from wild-type mice primed with L3 into T-cell-deficient mice. We found that mice reconstituted with primed T cells cleared intraperitoneal infections with infective larvae in an accelerated manner. To determine the components that may be responsible for the memory response, we transferred unfractionated T cells or purified CD4+ T cells or CD8+ T cells from BALB/cByJ mice primed a month earlier with L3 into T-cell-deficient BALB/c TCRbeta-/- mice. Recipients were challenged 10 days after adoptive transfer. Our data demonstrated that while either CD4+ or CD8+ T cells are able to confer some level of protection, both are required for an optimal recall response. To evaluate the longevity of the memory response, we primed several groups of wild-type mice at different times over a year. These mice were then challenged with a single injection of B. pahangi L3. The gap between the priming and second injections of larvae ranged between 4 and 60 weeks. We found that the memory responses in BALB/cByJ mice lasted over a year whereas those in C57BL/6 mice waned more rapidly.

Acute but not chronic macrophage recruitment in filarial infections in mice is dependent on C-C chemokine ligand 2.

Macrophages play an important role in the formation of granulomas and the clearance of Brugia pahangi infections in mice. However, the factors responsible for the recruitment of these cells to the site of infection are not known. In this study we examined the role of the C-C chemokine ligand 2 (CCL2; also known as macrophage chemotactic factor - MCP1) in macrophage recruitment in intraperitoneal infections with B. pahangi. We observed that CCL2 was expressed by peritoneal exudate cells and was present in the sera of wild-type mice. Serum levels of CCL2 peaked twice during the immune response, once during the early, acute phase and again during the late, chronic phase. To further elucidate the role of this chemokine in the anti-filarial immune response, we compared CCL2 deficient (CCL2(-/-)) mice to wild-type mice. We observed that macrophage recruitment was impaired only during the acute phase in the former. While macrophage recruitment was unaffected during the chronic phase, increased accumulation of B and T lymphocytes was seen in these mice. We further report that larval clearance and the in vitro adhesion of PECs to larvae were unimpaired in these mice.

Tick modulation of the in-vitro expression of adhesion molecules by skin-derived endothelial cells.

As a tick feeds, its saliva induces innate and acquired immune responses in the host, including leucocyte infiltration into the bite site. Tick salivary glands produce molecules, however, that counteract many host defences against blood feeding. The effects of salivary-gland extracts (SGE) of Dermacentor andersoni and Ixodes scapularis on the expression of various adhesion molecules [E-selectin, P-selectin, intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1)] by the sEND.1 cell line (which is based on cells from the subcutaneous tissue of mice) have now been investigated in vitro. The effects were found to differ with the tick species. The SGE of D. andersoni significantly down-regulated the expression of ICAM-1, whereas a similar extract prepared from I. scapularis significantly reduced the expression of P-selectin and VCAM-1. Tick salivary proteins therefore appear to have direct effects on adhesion-molecule expression, in addition to their previously established roles in down-regulating the pro-inflammatory cytokines that activate endothelial cells. It remains unclear exactly how the reduction of adhesion-molecule expression in the host's endothelial cells benefits the feeding tick but it may alter leucocyte migration to the bite site and/or reduce antigen presentation by the endothelial cells. It may also modulate the interactions between the host's leucocytes and any tick-borne pathogens, during initial infection of the endothelium.

Murine extramedullary erythropoiesis induced by tick infestation.

Tick saliva contains molecules that modulate the haemostasis, pain/itch responses, wound healing and immune defences of the host. Using BALB/c mice that were each infested with 10 nymphs of Dermacentor andersoni Stiles (Acari: Ixodidae), an attempt has now been made to determine the influence of tick infestation on the expression of leucocyte adhesion molecules in the host. The ticks became fully engorged by the fourth to sixth day of infestation. On the fourth day of infestation, the results of flow cytometry indicated that 2% of the host's splenocytes were expressing high levels of CD49 (alpha4 integrin of VLA-4) and low levels of CD11a (alphaL subunit of the integrin LFA-1). By the eighth day of infestation, 30% of the hosts' splenocytes had this phenotype and were negative for the lineage markers CD3e (T-lymphocytes), DX5 (natural-killer cells of a BALB/c lineage), B220 (B-lymphocytes), CD11b (monocytes/macrophages, granulocytes, natural-killer cells, activated T-lymphocytes, and B-1 cells) and CD11c (myeloid and splenic dendritic cells). Histological examination of the spleens from infested mice revealed disruption of the white-pulp/red-pulp demarcations and the presence of a large number of basophilic normoblasts. The CD11a(lo) population of splenocytes from the tick-infested mice was positive for TER-119 but negative for CD3, B220, CD11b and Gr, confirming that the splenocytes were members of the erythroid lineage. These results indicate that, within 8 days of their initiation, the tick infestations induced extramedullary erythropoiesis in the spleens of their murine hosts.