Dogs develop a broad spectrum of immune responses to infection by Leishmania. At either end of this spectrum we would find:

• A protective response, which is based on the production of IFN γ, IL-2 and TNF-α by T cells; cytokines which induce an activation of the macrophages and enhance their anti-Leishmania activity.
• An ineffective response, associated with a weak interferon production and probably increased production of IL-10 and other immunosuppressor cytokines (Alvar et al 2004, Baneth et al, 2008; Hosein et al 2016).

Subclinical infection is not always permanent, and factors such as an immunosuppressor treatment or a concomitant disease can change the balance between infection and immune response and lead to the development of the clinical disease. It is also unknown why some dogs are resistant to developing the disease while others are susceptible. There is clear evidence, however, which points to genetics playing an essential part. Some breeds of dog, like the boxer, cocker spaniel, Rottweiler and German shepherd, seem more susceptible to developing the disease (Sideris et al, 1999; Franca-Silva et al, 2003; Baneth et al, 2008), while others, like the Ibizan hound, very rarely develop clinical signs (Solano-Gallego et al, 2000).