The influence of the site of parasite inoculation on the development of Th1 and Th2 type immune responses in (BALB/c × C57BL/6) F1 mice infected with Leishmania major

Abstract

Although inbred strains of mice are classified as genetically resistant or susceptible to Leishmania major based upon their ability to control infection, other factors such as the strain, dose, and site of parasite inoculation can also affect the outcome of the disease. Here we used the F1 progeny of BALB/c (susceptible) and C57BL/6 (resistant) mice (designated CB6F1) to investigate whether mice or intermediate susceptibility to infection differed from the parental strains in their ability to control infections at different cutaneous sites. CB6F1 mice developed progressive disease when inoculated in the dorsal skin, but healed infections in the footpad. Consistent with these observations, mice inoculated in the footpad ultimately developed Th1 responses, known to be required for healing, while Th2 responses developed in mice inoculated in the dorsal skin. However, IL-4 and IFN-gamma production during the first few weeks of infection was similar in CB6F1 mice inoculated at either site, suggesting that factors in addition to the relative levels of these cytokines produced early in infection may influence the nature of the antileishmanial immune response, and the eventual disease outcome. Infection in CB6F1 mice provides a model for the study of immunity to L. major in genetically identical animals, in which a prolonged mixed Th1/Th2 cytokine pattern initially develops, but ultimately diverges into more defined Th1 and Th2 type responses.

Immunization of BALB/c Mice with KilledNeospora caninumTachyzoite Antigen Induces a Type 2 Immune Response and Exacerbates Encephalitis and Neurological Disease

“…Why nonionic surfactant vesicles were unsuccessful as an adjuvant for NSO to induce a type 1 immune response in the current study was not determined. Previous studies have shown that the use of high doses of antigen and the subcutaneous inoculation route, as carried out in the current study, can result in a bias toward disease-enhancing type 2 responses (13,17,26), regardless of the adjuvant used. A similar phenomenon could be occurring in N. caninum immunizations.…”

Conditions Influencing the Efficacy of Vaccination with Live Organisms againstLeishmania majorInfection

“…Prior studies have suggested that the site of primary infection can influence the outcome of disease and the Th1/Th2 balance of the primary immune response (3,9,26,27). In addition, Kirkpatrick et al have shown that the site of primary infection involving different intradermal sites on the back can influence the severity of the primary lesion and the resolution of a secondary lesion following reexposure to L. major (18).…”

Control of Infection withLeishmania majorin Susceptible BALB/c Mice Lacking the Common γ-Chain for FcR Is Associated with Reduced Production of IL-10 and TGF-β by Parasitized Cells

“…Leishmania-specific Ab was determined by ELISA based on a previously described assay (23). Briefly, polystyrene microtiter plates (Dynatech Laboratories) were coated with 1.0 g of L. major Ag (SLA) per ml in PBS (pH 7.4) overnight at 4°C.…”