This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nabors, G S Articles by Farrell, J P Search for Related Content PubMed PubMed Citation Articles by Nabors, G S Articles by Farrell, J P

research-article

Site-specific immunity to Leishmania major in SWR mice: the site of infection influences susceptibility and expression of the antileishmanial immune response.

Department of Pathobiology, University of Pennsylvania-School of Veterinary Medicine, Philadelphia 19104.

ABSTRACT

Inbred strains of mice usually develop either of two divergent patterns of infection in response to Leishmania major. Resistant mice, which develop self-limiting infections, respond immunologically with the activation of gamma interferon-secreting Th1 helper T cells, while nonhealing infections in susceptible mice are characterized by the proliferation of interleukin-4-secreting Th2 cells. Development of these divergent responses is dependent primarily on the strain of mouse infected, although factors such as the infective dose, species, and strain of parasite can also influence the degree of resistance. In this study, we show that a single mouse strain, SWR, can develop totally divergent patterns of infection depending on the site of parasite inoculation. Both SWR mice and highly susceptible BALB/c mice developed progressive, ultimately fatal disease when inoculated in the dorsal skin over the base of the tail. However, SWR mice infected in the hind footpad developed far less severe infections, which were for the most part controlled, whereas BALB/c mice infected in this site developed severe, nonhealing lesions. Production of gamma interferon and interleukin-4 and measurement of immunoglobulin E levels in serum were used to assess the degree of Th1 and Th2 cell activation in infected mice. Cytokine profiles early in infection had characteristics of a mixed Th1-Th2 response and were similar in SWR mice infected at either site. These early cytokine responses were not predictive of the ultimate disease outcome, since lymph node cells from healing mice eventually produced higher levels of gamma interferon than did those from nonhealing mice, and healing mice had lower levels of immunoglobulin E in serum, suggesting a functional bias toward Th1 cell activity in these animals. The differential ability of SWR mice to heal infections at different cutaneous sites provides a new model for the study of resistance to cutaneous leishmaniasis. Unlike traditional models of infection in which resistant and susceptible strains of mice are compared, this model allows for the study of factors that contribute to healing and nonhealing infections in a genetically identical strain of mouse.

This article has been cited by other articles:

• Rosas, L. E., Keiser, T., Barbi, J., Satoskar, A. A., Septer, A., Kaczmarek, J., Lezama-Davila, C. M., Satoskar, A. R. (2005). Genetic background influences immune responses and disease outcome of cutaneous L. mexicana infection in mice. Int Immunol 17: 1347-1357 [Abstract] [Full Text]  
• Tabbara, K. S., Peters, N. C., Afrin, F., Mendez, S., Bertholet, S., Belkaid, Y., Sacks, D. L. (2005). Conditions Influencing the Efficacy of Vaccination with Live Organisms against Leishmania major Infection. Infect. Immun. 73: 4714-4722 [Abstract] [Full Text]  
• Baldwin, T. M., Elso, C., Curtis, J., Buckingham, L., Handman, E. (2003). The Site of Leishmania major Infection Determines Disease Severity and Immune Responses. Infect. Immun. 71: 6830-6834 [Abstract] [Full Text]  
• Streit, J. A., Recker, T. J., Filho, F. G., Beverley, S. M., Wilson, M. E. (2001). Protective Immunity Against the Protozoan Leishmania chagasi Is Induced by Subclinical Cutaneous Infection with Virulent But Not Avirulent Organisms. J. Immunol. 166: 1921-1929 [Abstract] [Full Text]  
• Terabe, M., Kuramochi, T., Ito, M., Hatabu, T., Sanjoba, C., Chang, K.-P., Onodera, T., Matsumoto, Y. (2000). CD4+ Cells Are Indispensable for Ulcer Development in Murine Cutaneous Leishmaniasis. Infect. Immun. 68: 4574-4577 [Abstract] [Full Text]  
• Guy, B., Fourage, S., Hessler, C., Sanchez, V., Millet, M. J. Q. (1998). Effects of the Nature of Adjuvant and Site of Parenteral Immunization on the Serum and Mucosal Immune Responses Induced by a Nasal Boost with a Vaccine Alone. CVI 5: 732-736 [Abstract] [Full Text]