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Full-Text Articles in Immunology and Infectious Disease
Dual Engagement Of The Nlrp3 And Aim2 Inflammasomes By Plasmodium-Derived Hemozoin And Dna During Malaria, Parisa Kalantari, Rosane B. Deoliveira, Jennie Chan, Yolanda Corbett, Vijay A. K. Rathinam, Andrea Stutz, Eicke Latz, Ricardo T. Gazzinelli, Douglas T. Golenbock, Katherine A. Fitzgerald
Dual Engagement Of The Nlrp3 And Aim2 Inflammasomes By Plasmodium-Derived Hemozoin And Dna During Malaria, Parisa Kalantari, Rosane B. Deoliveira, Jennie Chan, Yolanda Corbett, Vijay A. K. Rathinam, Andrea Stutz, Eicke Latz, Ricardo T. Gazzinelli, Douglas T. Golenbock, Katherine A. Fitzgerald
Katherine A. Fitzgerald
Hemozoin (Hz) is the crystalline detoxification product of hemoglobin in Plasmodium-infected erythrocytes. We previously proposed that Hz can carry plasmodial DNA into a subcellular compartment that is accessible to Toll-like receptor 9 (TLR9), inducing an inflammatory signal. Hz also activates the NLRP3 inflammasome in primed cells. We found that Hz appears to colocalize with DNA in infected erythrocytes, even before RBC rupture or phagolysosomal digestion. Using synthetic Hz coated in vitro with plasmodial genomic DNA (gDNA) or CpG oligodeoxynucleotides, we observed that DNA-complexed Hz induced TLR9 translocation, providing a priming and an activation signal for inflammasomes. After phagocytosis, Hz and …
Dengue Virus Nonstructural Protein Ns5 Induces Interleukin-8 Transcription And Secretion, Carey L. Medin, Katherine A. Fitzgerald, Alan L. Rothman
Dengue Virus Nonstructural Protein Ns5 Induces Interleukin-8 Transcription And Secretion, Carey L. Medin, Katherine A. Fitzgerald, Alan L. Rothman
Alan Rothman
Elevated circulating levels of chemokines have been reported in patients with dengue fever and are proposed to contribute to the pathogenesis of dengue disease. To establish in vitro models for chemokine induction by dengue 2 virus (DEN2V), we studied a variety of human cell lines and primary cells. DEN2V infection of HepG2 and primary dendritic cells induced the production of interleukin-8 (IL-8), RANTES, MIP-1alpha, and MIP-1beta, whereas only IL-8 and RANTES were induced following dengue virus infection of HEK293 cells. Chemokine secretion was accompanied by an increase in steady-state mRNA levels. No chemokine induction was observed in HEK293 cells treated …
T Cell Receptor Vbeta Gene Usage In Thai Children With Dengue Virus Infection, Susan J. Gagnon, Anita M. Leporati, Sharone Green, Siripen Kalayanarooj, David W. Vaughn, Henry A. F. Stephens, Saroj Suntayakorn, Ichiro Kurane, Francis A. Ennis, Alan L. Rothman
T Cell Receptor Vbeta Gene Usage In Thai Children With Dengue Virus Infection, Susan J. Gagnon, Anita M. Leporati, Sharone Green, Siripen Kalayanarooj, David W. Vaughn, Henry A. F. Stephens, Saroj Suntayakorn, Ichiro Kurane, Francis A. Ennis, Alan L. Rothman
Sharone Green
T lymphocyte activation during dengue is thought to contribute to the pathogenesis of dengue hemorrhagic fever (DHF). We examined the T cell receptor Vbeta gene usage by a reverse transcriptase-polymerase chain reaction assay during infection and after recovery in 13 children with DHF and 13 children with dengue fever (DF). There was no deletion of specific Vbeta gene families. We detected significant expansions in usage of single Vbeta families in six subjects with DHF and three subjects with DF over the course of infection, but these did not show an association with clinical diagnosis, viral serotype, or HLA alleles. Differences …
Prediction Of Dengue Disease Severity Among Pediatric Thai Patients Using Early Clinical Laboratory Indicators, James A. Potts, Robert V. Gibbons, Alan L. Rothman, Anon Srikiatkhachorn, Stephen J. Thomas, Pra-On Supradish, Stephenie C. Lemon, Daniel H. Libraty, Sharone Green, Siripen Kalayanarooj
Prediction Of Dengue Disease Severity Among Pediatric Thai Patients Using Early Clinical Laboratory Indicators, James A. Potts, Robert V. Gibbons, Alan L. Rothman, Anon Srikiatkhachorn, Stephen J. Thomas, Pra-On Supradish, Stephenie C. Lemon, Daniel H. Libraty, Sharone Green, Siripen Kalayanarooj
Sharone Green
BACKGROUND: Dengue virus is endemic in tropical and sub-tropical resource-poor countries. Dengue illness can range from a nonspecific febrile illness to a severe disease, Dengue Shock Syndrome (DSS), in which patients develop circulatory failure. Earlier diagnosis of severe dengue illnesses would have a substantial impact on the allocation of health resources in endemic countries. METHODS AND FINDINGS: We compared clinical laboratory findings collected within 72 hours of fever onset from a prospective cohort children presenting to one of two hospitals (one urban and one rural) in Thailand. Classification and regression tree analysis was used to develop diagnostic algorithms using different …
Dengue Virus Nonstructural Protein Ns5 Induces Interleukin-8 Transcription And Secretion, Carey L. Medin, Katherine A. Fitzgerald, Alan L. Rothman
Dengue Virus Nonstructural Protein Ns5 Induces Interleukin-8 Transcription And Secretion, Carey L. Medin, Katherine A. Fitzgerald, Alan L. Rothman
Katherine A. Fitzgerald
Elevated circulating levels of chemokines have been reported in patients with dengue fever and are proposed to contribute to the pathogenesis of dengue disease. To establish in vitro models for chemokine induction by dengue 2 virus (DEN2V), we studied a variety of human cell lines and primary cells. DEN2V infection of HepG2 and primary dendritic cells induced the production of interleukin-8 (IL-8), RANTES, MIP-1alpha, and MIP-1beta, whereas only IL-8 and RANTES were induced following dengue virus infection of HEK293 cells. Chemokine secretion was accompanied by an increase in steady-state mRNA levels. No chemokine induction was observed in HEK293 cells treated …
Lps-Tlr4 Signaling To Irf-3/7 And Nf-Kappab Involves The Toll Adapters Tram And Trif, Katherine A. Fitzgerald, Daniel C. Rowe, Betsy J. Barnes, Daniel R. Caffrey, Alberto Visintin, Eicke Latz, Brian G. Monks, Paula M. Pitha, Douglas T. Golenbock
Lps-Tlr4 Signaling To Irf-3/7 And Nf-Kappab Involves The Toll Adapters Tram And Trif, Katherine A. Fitzgerald, Daniel C. Rowe, Betsy J. Barnes, Daniel R. Caffrey, Alberto Visintin, Eicke Latz, Brian G. Monks, Paula M. Pitha, Douglas T. Golenbock
Katherine A. Fitzgerald
Toll-IL-1-resistance (TIR) domain-containing adaptor-inducing IFN-beta (TRIF)-related adaptor molecule (TRAM) is the fourth TIR domain-containing adaptor protein to be described that participates in Toll receptor signaling. Like TRIF, TRAM activates interferon regulatory factor (IRF)-3, IRF-7, and NF-kappaB-dependent signaling pathways. Toll-like receptor (TLR)3 and 4 activate these pathways to induce IFN-alpha/beta, regulated on activation, normal T cell expressed and secreted (RANTES), and gamma interferon-inducible protein 10 (IP-10) expression independently of the adaptor protein myeloid differentiation factor 88 (MyD88). Dominant negative and siRNA studies performed here demonstrate that TRIF functions downstream of both the TLR3 (dsRNA) and TLR4 (LPS) signaling pathways, whereas the …