The effect of protein restriction on the development of protective immunity to Leishmania mexicana

Abstract

Protein deprived C57BL/6 mice infected with 10(3) amastigotes of Leishmania mexicana showed early arrest of lesion progression during the first 5 weeks of infection with subsequent development of progressive non-healing lesions. In contrast, well nourished mice similarly infected developed gradual healing lesions. The early resistance of malnourished mice to 10(3) amastigotes was overcome by a larger dose. After a primary inoculation with 10(3) amastigotes protein deprived mice failed to express protective immunity to a challenge inoculum given at 5 weeks of infection. When challenge was delayed until 10 weeks, protein deprived mice developed lesions at the site of challenge which tended to regress but were unable to manifest the high level of protective immunity seen in normally nourished reinfected controls. A challenge infection given at 5 or 10 weeks prejudiced the control of primary lesions particularly in the group of protein deprived mice challenged at 10 weeks. Equivalent levels of specific delayed hypersensitivity responses were found in protein deprived and normally nourished uninfected mice immunized with killed parasites which imply that the impaired protective immunity observed in protein deprived mice is not due to a deleterious effect of protein deprivation on the ability of the host to develop cellular responses such as delayed type hypersensitivity to Leishmania antigens.

Protein Malnutrition Impairs the Immune Response and Influences the Severity of Infection in a Hamster Model of Chronic Visceral Leishmaniasis

“…In the present hamster model, chronic infection by L. infantum induced a decline in T-cell functionality similar in severity to that caused by protein malnutrition, but this condition plus infection dramatically reduced T cell functionality, as reported in a cutaneous leishmaniasis mice model [37]. The humoral immune response was also affected by protein malnutrition, manifested in the form of B cell depletion.…”

“…Although Leishmania infection is known to impair the immune system [5], [36], only two studies have examined the adaptative immune response to Leishmania in conjunction with protein restriction. Malafaia et al [7] reported a reduction in IFN-γ production from SLA-stimulated splenocytes in malnourished mice infected with L. chagasi for 4 weeks, while Perez et al [37] found that protein-deprived mice infected with L. mexicana showed a depressed DTH response and a low in vitro splenic cell response to SLA and mitogens. In the present work, the 14%INF animals showed a patent specific cellular response, while the 3%INF animals showed an impaired response to leishmanial antigen and lower lymphocyte counts, particularly of CD4 + T cells.…”

Protein‐energy malnutrition as a risk factor for visceral leishmaniasis: a review

“…In the case of CL, some studies have demonstrated the influence of PEM on the course of the disease (34–37). Pérez et al.…”

Antigenic dietary protein guides maturation of the host immune system promoting resistance to Leishmania major infection in C57BL/6 mice

“…48 Studies from other groups confirm the influence of protein malnutrition on effective immune responses to Leishmania infection. 49 These authors used a diet with as little as 3% protein content, and the animals showed all the signs of malnutrition. In our model, dietary proteins were not simply removed or reduced; they were replaced by equivalent amounts of amino acids.…”