Inhibition of receptor tyrosine kinases restores immunocompetence and improves immune-dependent chemotherapy against experimental leishmaniasis in mice
Jane E Dalton, Asher Maroof, Benjamin MJ Owens, Priyanka Narang, Katherine Johnson, Najmeeyah Brown, Lovisa Rosenquist, Lynette Beattie, Mark Coles, Paul M Kaye
Journal of Clinical Investigation | AMER SOC CLINICAL INVESTIGATION INC | Published : 2010
Receptor tyrosine kinases are involved in multiple cellular processes, and drugs that inhibit their action are used in the clinic to treat several types of cancer. However, the value of receptor tyrosine kinase inhibitors (RTKIs) for treating infectious disease has yet to be explored. Here, we have shown in mice that administration of the broad-spectrum RTKI sunitinib maleate (Sm) blocked the vascular remodeling and progressive splenomegaly associated with experimental visceral leishmaniasis. Furthermore, Sm treatment restored the integrity of the splenic microarchitecture. Although restoration of splenic architecture was accompanied by an increase in the frequency of IFN-gamma+CD4+ T cells,..View full abstract
Awarded by Medical Research Council
This work was funded by grants from the British Medial Research Council and the Wellcome Trust. The authors thank the staff of the Department of Biology Technology Facility and Biological Services Facility for their expert assistance, Dimitris Kioussis and Nicky Harker for providing Rorc<SUP>-/-</SUP> mice, and Charles Lacey for comments on the manuscript.