Pathogenesis and Disease Transmission


In natural conditions, low numbers of promastigotes (100-1000) are transmitted by sand flies, which are sufficient to induce infection in susceptible dogs. Interestingly, infected sand flies are known to require more blood feedings from different animals. As a consequence, the sand fly sucks less blood from a single vertebrate and therefore attacks additional mammals, spreading the Leishmania parasites to a wider range of hosts.

Most parasites are killed by complement factors of the vertebrate host, but a few survive, using different strategies. The promastigotes adhere to resident or recruited cells of the monocyte / macrophage lineage. Complement-dependent adhesion is followed by internalization through phagocytosis. Inside the phagolysosomes, the promastigotes transform into non-motile amastigotes, accompanied by a rapid drop in pH to ~5.

In a susceptible host, dissemination from the skin to lymph nodes, spleen and bone marrow takes place within the first few hours. In resistant animals, parasites remain localized in the skin or at maximum in the local lymph node.

Protective immune response requires the presentation of appropriate antigens by antigen-presenting cells (APCs; macrophages, dendritic and Langerhans' cells most important in leishmaniosis), the induction and expansion CD4+ Th1-lymphocytes, and the activation of macrophages for efficient parasite killing. Superoxide (O2-) and nitric oxide (NO) are the two major effector mechanisms for eliminating Leishmania parasites.

The type of immune response (Th1 or Th2) is determined mainly by the cytokine milieu that the T cells face when they first encounter the antigen, with IL-4 being most important. Early up-regulation of IL-4 is seen in susceptible animals subsequently inducing IL-12 unresponsiveness. Overall, the central decisive element in the development of susceptibility or resistance after Leishmania infection appears whether CD4+ T cells remain responsive to IL-12 by remaining expression of the IL-12 receptor for more than 48 hours following infection. In susceptible dogs during the course of infection, T-lymphocyte regions become cell-depleted and B-cell regions proliferate.
Potential hazard has further been observed by large amounts of circulating immune complexes (CICs). Autoantibodies against erythrocytes, thrombocytes and nuclear proteins have also been documented.


With macrophages as main cellular type for promastigotes the parasite has chosen a cell type which normally is playing an important role in the induction as well as expression of an immune response. How the parasites are actually managing this paradoxon is not completely clarified.

After different periods of incubation (2-12 months) dogs may either develop clinical signs that are often fatal or they might develop resistance to infection. The latter was found to be associated with a strong parasite-specific cellular immune response and the production of cytokines such as IL-2 and TNF. Dogs may furthermore develop transient, self-limiting infections. They may also spontaneously convert from seropositive infected to negative dogs or do not develop antibodies at all.

Immune responses to Leishmania may result in a polarization of T cell activity towards a distinct helper T (Th) phenotype. The cytokines produced may activate effector mechanisms that can result in either protective immunity or exacerbation of the disease (Pinelli et al., 1999). Infected macrophages rely mainly on nitric oxide production as an innate mechanism of killing Leishmania. The parasite inhibits this mechanism, and is able to multiply in the parasitophorous vacuole. Eventually infected macrophages rupture, and amastigotes are taken up by new phagocytic cells. Macrophages and dendritic cells present Leishmania antigens to T cells, and either an effective cellular immune response results (a Th1 pattern) or an ineffective humoral response occurs (Th2 pattern). Although several factors influence the development of T helper cell subsets, the most important one may be their early exposure to cytokines (Pinelli et al., 1999).



  • Ferrer, L.: The pathology of canine leishmaniasis. In: Killick-Kendrick, R. (ed.): Canine leishmaniasis: moving towards a solution. Proc. 2nd Int. Can. Leishm. Forum, Sevilla, Spain, Intervet Int., Boxmeer, The Netherlands, 2002, 21-24

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