Pathology Diagnosis and Treatment

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s13071-019-3402-2

10.1111/1755-0998.12556

**100**

**103**

**Chapter 8**

**Abstract**

resistance.

**1. Introduction**

Wnt5A Signaling Antagonizes

*Leishmania donovani* Infection

Infection by the parasite *Leishmania donovani* causes Visceral Leishmaniasis, a deadly disease if not properly treated. *L. donovani* captures the immune defense potential of host macrophages. It disrupts immune homeostasis at least partly by inducing expression of anti-inflammatory cytokines and altering the cellular cytoskeletal framework, thereby creating a niche for its own survival. While inhibition of macrophage Wnt5A signaling promotes infection by the parasite, activation of Wnt5A signaling significantly dampens infection. Experimental evidence suggests that the antagonistic effect of Wnt5A signaling on parasite infection in macrophages may be on account of its influence on the actin cytoskeleton. Importantly, the inhibitory effect of Wnt5A on infection is sustained independent of drug sensitivity and resistance. Keeping in mind that drugs used to treat Visceral Leishmaniasis are quite toxic and the parasite develops drug resistance, revamping host Wnt5A signaling may be useful for eliminating infection independent of drug sensitivity or

*Arijit Chakraborty, Shreyasi Maity and Malini Sen*

**Keywords:** Wnt5A, *L. donovani*, macrophage, cytoskeleton, Rac1, actin

wall of the central vein, and pericellular fibrosis [4].

Leishmaniasis is a group of neglected tropical zoonotic diseases caused by intracellular obligate parasites belonging to the genus *Leishmania*. The disease is endemic to about 60 countries and may turn out life threatening if not properly treated [1]. Clinical manifestations of the disease range from cutaneous lesions (as in Cutaneous Leishmaniasis) to visceral pathologies (as in Visceral Leishmaniasis) [2]. In this review we will focus on Visceral Leishmaniasis (VL), its causative organism *Leishmania donovani* and host immune response to *L. donovani* infection.

Like many other intracellular parasites, *L. donovani* has evolved a unique ability to sustain a parasitic mode of life. In VL, *L. donovani* resides and then proliferates mainly in the spleen, the liver and the bone marrow. This can cause splenomegaly, hepatomegaly, fever and gray discoloration of the skin—hence the name "kala azar" or "black disease". Associated hematological changes include a hemoglobin level of 7–10 g/dl, leukopenia, thrombocytopenia, pancytopenia, increased ESR and erythroid hyperplasia in the bone marrow and varying degrees of erythrophagocytosis, leukophagocytosis and granulomatous reactions. In some cases clotting abnormalities and deranged platelet function are also observed [3]. Few studies, furthermore, indicate inflammatory changes in the liver, which include hypertrophy and hyperplasia of Kupffer cells, diffused intralobular fibrosis, fibrosis of the
