Acute immobilization stress induces clinical and neuroimmunological alterations in experimental murine cutaneous leishmaniasis

Abstract

BACKGROUND: The skin is an important component of the neuroendocrine-immune axis. Several studies have shown that stress exacerbates skin disorders, affecting the function of sebaceous glands, keratinocytes, epidermal Langerhans cells and other cells, having an impact on the pathogenesis of many immunologically associated skin diseases. In American cutaneous leishmaniasis, we have shown the importance of the epidermis as a regulatory site, with the key participation of Langerhans cells. OBJECTIVES: To analyse the effect of acute immobilization stress on Langerhans cells, substance P (SP), calcitonin gene-related peptide (CGRP) and the natural course of infection in a murine model of cutaneous leishmaniasis. METHODS: BALB/c mice, susceptible to Leishmania infection, were placed under acute stress by immobilization (confinement) for 2 or 8 h before inoculation with L. mexicana (MHOM/BZ/82/BEL21). An avidin-biotin immunoperoxidase technique was used for cell and neuropeptide identification. RESULTS: The stressed animals became more susceptible to the parasite infection, which was manifested by acceleration and exacerbation of the lesions. In addition, the stressed animals showed morphological alterations (spherical bodies and shortened dendrites) and decreased numbers of epidermal Langerhans cells, when compared with control L. mexicana-infected mice. Mice stressed for 8 h showed greater and antidromic immunoreactivity to CGRP and SP at the time of infection. Moreover, the single inoculation of parasites caused a decrease of CGRP innervation. CONCLUSIONS: Acute immobilization stress induces an immunosuppressive state that further favours Leishmania invasion in susceptible animals.