Type 1 diabetes and parasite infection: an exploratory study in the NOD mouse

Microorganisms have long been suspected to influence the outcome of immune-related syndromes, particularly autoimmune diseases. Type 1 diabetes (T1D) results from the autoimmune destruction of the pancreatic islets’ insulin-producing beta cells, causing high glycemia levels. Genetics is part of its etiology, but environmental factors, particularly infectious microorganisms, also play a role.

It was shown that bacteria, viruses, and parasites, influence the outcome of T1D in mice and humans. We have used the Non-Obese Diabetic (NOD) mouse that spontaneously develops T1D to address the influence of a parasitic infection, leishmaniasis. Leishmania amazonensis are intracellular eukaryotic parasites replicating predominantly in macrophages and are responsible for cutaneous leishmaniasis. The implication of Th1 immune responses in T1D and leishmaniasis led us to study this parasite in the NOD mouse model. We have previously constructed osteopontin knockout mice in an NOD genetic background and demonstrated that this protein plays a role in the T1D phenotype. In addition, osteopontin (OPN) has been found i) to play a role in the immune response to various infectious microorganisms and ii) to be implicated in other autoimmune conditions, such as multiple sclerosis in humans and experimental autoimmune encephalomyelitis (EAE) in mice.

We present herein data demonstrating the implication of OPN in the response to Leishmania in the NOD mouse and the influence of this parasitic infection on T1D. This exploratory study aims to investigate the environmental infectious component of the autoimmune response, including through Th1 immunity, common to both T1D and leishmaniasis.