Immunopathogenic mechanisms of non-healing cutaneous leishmaniasis caused by Leishmania amazonensis infection

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dc.contributor.advisorLynn Soongen_US
dc.contributor.committeeMemberVictor E Reyesen_US
dc.contributor.committeeMemberRichard G Titusen_US
dc.contributor.committeeMemberGary R Klimpelen_US
dc.contributor.committeeMemberAllan R Brasieren_US
dc.creatorNanchaya Wanasenen_US
dc.date.accessioned2011-12-20T16:04:38Z
dc.date.available2009-06-09en_US
dc.date.available2011-12-20T16:04:38Z
dc.date.created2007-04-26en_US
dc.date.issued2007-04-10en_US
dc.description.abstractThe objective of my dissertation project is to understand mechanisms employed by Leishmania amazonensis to evade host immune components, particularly B cells and interferon-gamma. Our data have shown that L. amazonensis infection induces B cell activation, leading to enhanced lesion development. In the absence of B cells, L. amazonensis-infected mice developed a delayed onset of disease, correlating with an impaired activation of antigen-specific pathogenic CD4+ T cells. Flow cytometry and immunohistochemical studies suggest that B cells may provide secondary signals for activating T helper cells and recruiting leukocytes to the site of infection. The pathogenic role of B cells was suggested to be partly due to the presence of antibodies, which induced dendritic cell activation and promoted efficient priming of parasite-specific T cells to produce high levels of IL-10. The investigation of the role of IFN-g in L. amazonensis infection revealed that IFN-g alone could promote parasite growth within macrophages (MFs) by inducing the expression of mouse cationic amino acid transporter-2B (mCAT-2B), a key transporter for L-arginine. Although a clear upregulation of mCAT-2B and L-arginine transport was detected, no measurable iNOS or arginase activities were observed in IFN-g-treated, infected MFs. These data suggest an involvement of a novel L-arginine usage independent of iNOS and arginase activities during IFN-g-mediated parasite growth enhancement. The ability to scavenge available L-arginine directly by the parasites is proposed. In addition to inducing pathogenic B cells and interfering with L-arginine pathways, these parasites were found to express molecules similar to the mammalian chemokine receptor, CCR5. Although the function of a parasite-derived CCR5-like molecule remains unclear, it may help the parasites to find immature “safe target” cells. Together, this project provides new insights into the complex interactions between the parasite and host immune system and indicates the challenges we will face in the control of non-healing cutaneous leishmaniasis.en_US
dc.format.mediumelectronicen_US
dc.identifier.otheretd-04262007-150805en_US
dc.identifier.urihttp://hdl.handle.net/2152.3/101
dc.language.isoengen_US
dc.rightsCopyright © is held by the author. Presentation of this material on the TDL web site by The University of Texas Medical Branch at Galveston was made possible under a limited license grant from the author who has retained all copyrights in the works.en_US
dc.subjectLeishmania amazonensisen_US
dc.subjectinterferon gammaen_US
dc.subjectCCR5en_US
dc.subjectB cellsen_US
dc.titleImmunopathogenic mechanisms of non-healing cutaneous leishmaniasis caused by Leishmania amazonensis infectionen_US
dc.type.genredissertationen_US
dc.type.materialtexten_US
thesis.degree.departmentMicrobiology and Immunologyen_US
thesis.degree.grantorThe University of Texas Medical Branchen_US
thesis.degree.levelDoctoralen_US
thesis.degree.namePhDen_US

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