Defining The Roles Of TNF, Lymphotoxin Alpha And LIGHT In Experimental Visceral Leishmaniasis
Funder
National Health and Medical Research Council
Funding Amount
$410,148.00
Summary
Visceral leishmaniasis (VL) is an important human disease caused by the protozoan parasites Leishmania donovani and L. infantum (chagasi). Studies in experimental VL caused by L. donovani infection of mice have resulted in major insights into the causes of VL and the reasons why VL patients become severely immunocompromised. Work from our laboratory has shown that members of the TNF family of cytokines play key roles in the generation of effective immune responses during VL, but also mediate sig ....Visceral leishmaniasis (VL) is an important human disease caused by the protozoan parasites Leishmania donovani and L. infantum (chagasi). Studies in experimental VL caused by L. donovani infection of mice have resulted in major insights into the causes of VL and the reasons why VL patients become severely immunocompromised. Work from our laboratory has shown that members of the TNF family of cytokines play key roles in the generation of effective immune responses during VL, but also mediate significant tissue pathology, particularly in the spleen, following L. donovani infection. In this grant, we will define the roles of several key members of the TNF family in the generation of immunity and pathology during experimental VL. We will also test if the activity of these molecules can be modulated to control disease without detrimental side effects. Results from this research have implication for the design of new vaccines and therapeutics to control VL. In addition, given the important role of TNF family members in cancers and autoimmune diseases, the work in this grant will have advance our understanding of pathogenic processes that are common to many important human diseases.Read moreRead less
Modulation Of Leishmaniasis By The Proinflammatory Cytokines TNF
Funder
National Health and Medical Research Council
Funding Amount
$288,911.00
Summary
We have established a mouse model that has been genetically modified and cannot produce the cytokine tumour necrosis factor. This cytokine is secreted in the beginning of the inflammatory response. If these mice are infected with a parasite they are not able to heal the infection and die quickly. We can demonstrate that these mice cannot regulate the beginning inflammatory response and do not form a cellular infiltrate at the site of infection.