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Academic Background

B.S.   (1975)  University of Michigan

M.D.  (1980)   University of Michigan

Internship and Residency, Internal Medicine (1980-1983) 

                         George Washington University Hospital

Infectious Diseases Fellowship (1984-1986)

             University of Wisconsin Hospitals and Clinics

Post-doctoral Fellowship (1986-1988)

             University of Wisconsin Hospitals and Clinics

             (Christian R.H. Raetz, mentor)

Post-doctoral Fellowship (1989-1990)

             Merck Research Laboratories, Rahway, NJ

             (Christian R.H. Raetz, mentor)

Assistant Professor of Medicine and Infectious Diseases (1990- 1995)

             Boston University School of Medicine

Associate Professor of Medicine and Infectious Diseases (1995-1999)

             Boston University School of Medicine

Professor of Medicine and Infectious Diseases (1999-2001)

             Boston University School of Medicine

Professor of Medicine and Infectious Diseases (2001-present)

              UMass Medical School

             Tenure award:  2004

           

Innate immunity and Infectious Diseases.Douglas Golenbock, MD

Dr. Douglas Golenbock is Chief of the Division of Infectious Diseases and Immunology in the Department of Medicine. He holds a joint appointment in the Department of Microbiology and Physiological Systems. The goal of his laboratory is to characterize phagocytic receptors that recognize the presence of microbes in the context of infectious illnesses. As the mechanisms of inflammation in infectious diseases are similar to those associated with sterile inflammation, we also study Alzheimer's Disease.    Virtually all of our work focuses on two groups of receptors: Toll-like receptors (TLRs) and Nod-like receptors (NLRs) in the context of the inflammasome.

 Our entry into the TLR field was heralded by the discovery that TLR4, and MD-2 mediate responses to bacterial endotoxin, a major cause of sepsis. More recently, we have begun to focus on intracellular nucleic acid receptors as regulators of IL-1 production and type I interferons. There are six major projects in the laboratory:

1. Defining the response to bacterial lipopolysaccharide (LPS, endotoxin). LPS immunologically potent amphipathic glycolipid on the surface of Gram-negative bacteria. It is thought to be responsible for Gram-negative sepsis. This project involves detailed studies of TLR4/MD-2 and adapter molecules that transduce an activation signal. The work is funded via an NIH merit award to Dr. Golenbock.

2. Characterizing the role of the LPS receptor system, in pelvic inflammatory disease. This project is based upon the realization that Neisseria gonorrhoeae mediates much of its inflammation via the TLR4/MD-2 signaling pathway and is funded via an NIH U19 award that includes other infectious diseases faculty, including Drs. Peter Rice (program PI) and Sanjay Ram.

3. Defining the innate immune response to P. falciparum malaria. Very little is known about how P. falciparum causes inflammation. We have developed several projects in this area, including basic investigations into nucleic acid receptors and inflammasomes. This is a large project that is a collaboration with two other UMass investigators, Drs. Kate Fitzgerald and Ricardo Gazzinelli. The project is funded via an RO1 to Drs. Golenbock and Fitzgerald.

4. Defining the innate immune response to Group B streptococcus. We have previously demonstrated that Group B streptococcus activates type I interferon production as a result of hemolysin expression, which allows DNA access to the phagocyte cytosolic compartment. Recent studies also implicate hemolysin as a mediator of NLRP3 activation via the effects of bacterial RNA. This project is a three way collaboration with a bacterial genetics group at the Institut Pasteur (France) headed by Dr. Patrick Trieu-Cuot and a cell biology group at the University of Freiburg (Germany) run by Dr. Philipp Henneke, a former Golenbock post-doctoral fellow, and is funded by an RO1 grant to Dr. Golenbock.

5. Defining a role for PSTPIP1. PSTPIP1 is a protein that causes an autoinflammatory disorder known as PAPA syndrome: Pogenic Arthritis, Pyoderma gangrenosum and Acne. The disease is due to dysregulation of IL-1 production that probably results from the activation on pyrin, the gene product associated with Familial Mediterranean Fever. Dr. Donghai Wang, a member of the Golenbock laboratory, has engineered mice that are either deficient in PSTPIP1, or that carry the known lesions of PAPA syndrome. It is funded by an R21 grant to Drs. Wang and Golenbock.

6. Examining the role of the NLRP3 inflammasome in Alzheimers Disease. Alzheimer (AD) is a chronic inflammatory disease that causes premature dementia and death. It appears to be caused, in part, by -amyloid, an insoluble protein that activates the NLRP3 inflammasome in microglial cells, resulting in neuronal cell death.

One of the major goals of the Golenbock lab and the Division of Infectious Diseases is to promote UMass immunology and the field of innate immunity in general. The Division has organized the state of the art meetng in the field of innate immunity. We have now had four Toll meetings: Toll2004 (Taormina, Italy), Toll2006 (Salvador, Brazil; www.toll2006.org), Toll2008 (Cascais, Portugal; www.toll2008.org) and Toll2011 (Riva del Garda, Italy; www.toll2011.org). Virtually all of the research faculty, students and post-docs in Infectious Diseases attend the Toll meetings, which typically involve ~ 600 participants.

For More information on Toll related meetings please see

 http://www.youtube.com/watch?v=2rqQOmkiL5o

For More information on Targeting a new therapy for Alzheimer's pleas see:

 http://www.youtube.com/watch?v=5LXshrNFkXA

 

One or more keywords matched the following items that are connected to Golenbock, Douglas
Item TypeName
Academic Article Toll-like receptor-4 mediates lipopolysaccharide-induced signal transduction.
Academic Article Lipopolysaccharide recognition, CD14, and lipopolysaccharide receptors.
Academic Article Cutting edge: cells that carry A null allele for toll-like receptor 2 are capable of responding to endotoxin.
Academic Article Cutting edge: recognition of Gram-positive bacterial cell wall components by the innate immune system occurs via Toll-like receptor 2.
Academic Article Human toll-like receptors mediate cellular activation by Mycobacterium tuberculosis.
Academic Article Toll-like receptor 2 functions as a pattern recognition receptor for diverse bacterial products.
Academic Article The CD14 ligands lipoarabinomannan and lipopolysaccharide differ in their requirement for Toll-like receptors.
Academic Article A novel synthetic acyclic lipid A-like agonist activates cells via the lipopolysaccharide/toll-like receptor 4 signaling pathway.
Academic Article Structure and function of Toll-like receptor proteins.
Academic Article Differential effects of a Toll-like receptor antagonist on Mycobacterium tuberculosis-induced macrophage responses.
Academic Article Membrane-associated proteins of a lipopolysaccharide-deficient mutant of Neisseria meningitidis activate the inflammatory response through toll-like receptor 2.
Academic Article Toll-like receptor 2-dependent inhibition of macrophage class II MHC expression and antigen processing by 19-kDa lipoprotein of Mycobacterium tuberculosis.
Academic Article Differential roles of TLR2 and TLR4 in the host response to Gram-negative bacteria: lessons from a lipopolysaccharide-deficient mutant of Neisseria meningitidis.
Academic Article Lipopolysaccharides from periodontopathic bacteria Porphyromonas gingivalis and Capnocytophaga ochracea are antagonists for human toll-like receptor 4.
Academic Article Cutting edge: Immune stimulation by neisserial porins is toll-like receptor 2 and MyD88 dependent.
Academic Article Innate immune recognition of lipopolysaccharide by endothelial cells.
Academic Article Induction of cytokine production in human T cells and monocytes by highly purified lipoteichoic acid: involvement of Toll-like receptors and CD14.
Academic Article Cutting edge: the immunostimulatory activity of the lung surfactant protein-A involves Toll-like receptor 4.
Academic Article Toll-like receptor (TLR) signaling in response to Aspergillus fumigatus.
Academic Article Lipopolysaccharide rapidly traffics to and from the Golgi apparatus with the toll-like receptor 4-MD-2-CD14 complex in a process that is distinct from the initiation of signal transduction.
Academic Article Dysregulation of LPS-induced Toll-like receptor 4-MyD88 complex formation and IL-1 receptor-associated kinase 1 activation in endotoxin-tolerant cells.
Academic Article Recognition of pneumolysin by Toll-like receptor 4 confers resistance to pneumococcal infection.
Academic Article IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway.
Academic Article Lysines 128 and 132 enable lipopolysaccharide binding to MD-2, leading to Toll-like receptor-4 aggregation and signal transduction.
Academic Article Adjuvants and their signaling pathways: beyond TLRs.
Academic Article Biological activities of Bacteroides forsythus lipoproteins and their possible pathological roles in periodontal disease.
Academic Article Relationship between structures and biological activities of mycoplasmal diacylated lipopeptides and their recognition by toll-like receptors 2 and 6.
Academic Article Non-mannose-capped lipoarabinomannan induces lung inflammation via toll-like receptor 2.
Academic Article Expression of functional TLR4 confers proinflammatory responsiveness to Trypanosoma cruzi glycoinositolphospholipids and higher resistance to infection with T. cruzi.
Academic Article Hepatitis C core and nonstructural 3 proteins trigger toll-like receptor 2-mediated pathways and inflammatory activation.
Academic Article Human lupus autoantibody-DNA complexes activate DCs through cooperation of CD32 and TLR9.
Academic Article Activation of toll-like receptor (TLR)2, TLR4, and TLR9 in the mammalian cornea induces MyD88-dependent corneal inflammation.
Academic Article The interferon regulatory factor, IRF5, is a central mediator of toll-like receptor 7 signaling.
Academic Article MyD88 is critical for the development of innate and adaptive immunity during acute lymphocytic choriomeningitis virus infection.
Academic Article Proinflammatory phenotype of vascular smooth muscle cells: role of efficient Toll-like receptor 4 signaling.
Academic Article Human cardiac inflammatory responses triggered by Coxsackie B viruses are mainly Toll-like receptor (TLR) 8-dependent.
Academic Article The apoptotic response to pneumolysin is Toll-like receptor 4 dependent and protects against pneumococcal disease.
Academic Article Toll-like receptor 2 mediates persistent chemokine release by Chlamydia pneumoniae-infected vascular smooth muscle cells.
Academic Article Toll-like receptor 2 mediates inflammatory cytokine induction but not sensitization for liver injury by Propioni- bacterium acnes.
Academic Article Human toll-like receptor 2 mediates monocyte activation by Listeria monocytogenes, but not by group B streptococci or lipopolysaccharide.
Academic Article Toll-like receptor 4 imparts ligand-specific recognition of bacterial lipopolysaccharide.
Academic Article Comparative toll-like receptor 4-mediated innate host defense to Bordetella infection.
Academic Article Meningococcal porin PorB binds to TLR2 and requires TLR1 for signaling.
Academic Article Gingipains inactivate a cell surface ligand on Porphyromonas gingivalis that induces TLR2-and TLR4-independent signaling.
Academic Article The biology of Toll-like receptors.
Academic Article A mechanism for neurodegeneration induced by group B streptococci through activation of the TLR2/MyD88 pathway in microglia.
Academic Article Pattern recognition receptors TLR4 and CD14 mediate response to respiratory syncytial virus.
Academic Article MD-2 expression is not required for cell surface targeting of Toll-like receptor 4 (TLR4).
Academic Article Toll-like receptor 4 mediates intracellular signaling without TNF-alpha release in response to Cryptococcus neoformans polysaccharide capsule.
Academic Article Toll-like receptor-dependent discrimination of streptococci.
Academic Article TLR9 and the recognition of self and non-self nucleic acids.
Academic Article A bacterial carbohydrate links innate and adaptive responses through Toll-like receptor 2.
Academic Article Innate immune responses to endosymbiotic Wolbachia bacteria in Brugia malayi and Onchocerca volvulus are dependent on TLR2, TLR6, MyD88, and Mal, but not TLR4, TRIF, or TRAM.
Academic Article Malaria hemozoin is immunologically inert but radically enhances innate responses by presenting malaria DNA to Toll-like receptor 9.
Academic Article Extolling the diversity of bacterial endotoxins.
Academic Article Toll-like receptor 9-dependent activation by DNA-containing immune complexes is mediated by HMGB1 and RAGE.
Academic Article Immunology. The shape of things to come.
Academic Article YopJ targets TRAF proteins to inhibit TLR-mediated NF-kappaB, MAPK and IRF3 signal transduction.
Academic Article Activation of TLR2 and TLR4 by glycosylphosphatidylinositols derived from Toxoplasma gondii.
Academic Article Activation of Toll-like receptor-2 by glycosylphosphatidylinositol anchors from a protozoan parasite.
Academic Article Molecular genetic analysis of an endotoxin nonresponder mutant cell line: a point mutation in a conserved region of MD-2 abolishes endotoxin-induced signaling.
Academic Article Phagocytosis and intracellular killing of MD-2 opsonized gram-negative bacteria depend on TLR4 signaling.
Academic Article Bacterial fimbriae stimulate proinflammatory activation in the endothelium through distinct TLRs.
Academic Article Lipoteichoic acid-induced lung inflammation depends on TLR2 and the concerted action of TLR4 and the platelet-activating factor receptor.
Academic Article Chlamydia pneumoniae and chlamydial heat shock protein 60 stimulate proliferation of human vascular smooth muscle cells via toll-like receptor 4 and p44/p42 mitogen-activated protein kinase activation.
Academic Article Induction of tolerance to lipopolysaccharide and mycobacterial components in Chinese hamster ovary/CD14 cells is not affected by overexpression of Toll-like receptors 2 or 4.
Academic Article Structural requirements of muramylpeptides for induction of Toll-like receptor 2-mediated NF-kappaB activation in CHO cells.
Academic Article TIRAP: how Toll receptors fraternize.
Academic Article TLR-independent type I interferon induction in response to an extracellular bacterial pathogen via intracellular recognition of its DNA.
Academic Article Malaria primes the innate immune response due to interferon-gamma induced enhancement of toll-like receptor expression and function.
Academic Article Recombinant Ov-ASP-1, a Th1-biased protein adjuvant derived from the helminth Onchocerca volvulus, can directly bind and activate antigen-presenting cells.
Academic Article Marked upregulation of cholesterol 25-hydroxylase expression by lipopolysaccharide.
Academic Article A TIR domain variant of MyD88 adapter-like (Mal)/TIRAP results in loss of MyD88 binding and reduced TLR2/TLR4 signaling.
Academic Article Mal connects TLR2 to PI3Kinase activation and phagocyte polarization.
Academic Article MyD88 adaptor-like is not essential for TLR2 signaling and inhibits signaling by TLR3.
Academic Article Novel engagement of CD14 and multiple toll-like receptors by group B streptococci.
Academic Article CD36 ligands promote sterile inflammation through assembly of a Toll-like receptor 4 and 6 heterodimer.
Academic Article LBP, CD14, TLR4 and the murine innate immune response to a peritoneal Salmonella infection.
Academic Article MD-2 residues tyrosine 42, arginine 69, aspartic acid 122, and leucine 125 provide species specificity for lipid IVA.
Academic Article Atherogenic lipids and lipoproteins trigger CD36-TLR2-dependent apoptosis in macrophages undergoing endoplasmic reticulum stress.
Academic Article Autophagy controls IL-1beta secretion by targeting pro-IL-1beta for degradation.
Academic Article Natural loss-of-function mutation of myeloid differentiation protein 88 disrupts its ability to form Myddosomes.
Academic Article Activation of the NLRP3 inflammasome by group B streptococci.
Academic Article Heme induces programmed necrosis on macrophages through autocrine TNF and ROS production.
Academic Article DOCK8 functions as an adaptor that links TLR-MyD88 signaling to B cell activation.
Academic Article An unconventional role for miRNA: let-7 activates Toll-like receptor 7 and causes neurodegeneration.
Academic Article Mediators of innate immune recognition of bacteria concentrate in lipid rafts and facilitate lipopolysaccharide-induced cell activation.
Academic Article Involvement of toll-like receptor (TLR) 2 and TLR4 in cell activation by mannuronic acid polymers.
Academic Article Cellular activation, phagocytosis, and bactericidal activity against group B streptococcus involve parallel myeloid differentiation factor 88-dependent and independent signaling pathways.
Academic Article A novel host-parasite lipid cross-talk. Schistosomal lyso-phosphatidylserine activates toll-like receptor 2 and affects immune polarization.
Academic Article Combined action of nucleic acid-sensing Toll-like receptors and TLR11/TLR12 heterodimers imparts resistance to Toxoplasma gondii in mice.
Academic Article Human cytomegalovirus activates inflammatory cytokine responses via CD14 and Toll-like receptor 2.
Academic Article The antifungal drug amphotericin B promotes inflammatory cytokine release by a Toll-like receptor- and CD14-dependent mechanism.
Academic Article Heat-killed Brucella abortus induces TNF and IL-12p40 by distinct MyD88-dependent pathways: TNF, unlike IL-12p40 secretion, is Toll-like receptor 2 dependent.
Academic Article Importance of extra- and intracellular domains of TLR1 and TLR2 in NFkappa B signaling.
Academic Article LPS-TLR4 signaling to IRF-3/7 and NF-kappaB involves the toll adapters TRAM and TRIF.
Academic Article Receptor "cross talk" in innate immunity.
Academic Article Cell distributions and functions of Toll-like receptor 4 studied by fluorescent gene constructs.
Academic Article TLR9 signals after translocating from the ER to CpG DNA in the lysosome.
Academic Article Haemophilus influenzae type b-outer membrane protein complex glycoconjugate vaccine induces cytokine production by engaging human toll-like receptor 2 (TLR2) and requires the presence of TLR2 for optimal immunogenicity.
Academic Article Dual role of TLR2 and myeloid differentiation factor 88 in a mouse model of invasive group B streptococcal disease.
Academic Article Innate immune responses to Rhodococcus equi.
Academic Article The induction of macrophage gene expression by LPS predominantly utilizes Myd88-independent signaling cascades.
Academic Article Stimulation of toll-like receptor 2 by Coxiella burnetii is required for macrophage production of pro-inflammatory cytokines and resistance to infection.
Academic Article Mechanisms of TLR9 activation.
Academic Article Cell activation by Toll-like receptors: role of LBP and CD14.
Academic Article Introduction: Toll receptors come of age.
Academic Article Endotoxin recognition and signal transduction by the TLR4/MD2-complex.
Academic Article Negative regulation of Toll-like receptor 4 signaling by the Toll-like receptor homolog RP105.
Academic Article Role of lipoteichoic acid in the phagocyte response to group B streptococcus.
Academic Article A Leptospira interrogans enzyme with similarity to yeast Ste14p that methylates the 1-phosphate group of lipid A.
Academic Article Of mice and man: TLR11 (finally) finds profilin.
Academic Article Pharmacological inhibition of endotoxin responses is achieved by targeting the TLR4 coreceptor, MD-2.
Academic Article Inhibition of TLR-4/MD-2 signaling by RP105/MD-1.
Academic Article The myristoylation of TRIF-related adaptor molecule is essential for Toll-like receptor 4 signal transduction.
Academic Article Trif-related adapter molecule is phosphorylated by PKC{epsilon} during Toll-like receptor 4 signaling.
Academic Article HMGB1 signals through toll-like receptor (TLR) 4 and TLR2.
Academic Article MyD88-dependent IL-1 receptor signaling is essential for gouty inflammation stimulated by monosodium urate crystals.
Academic Article MD-2.
Academic Article Flavivirus activation of plasmacytoid dendritic cells delineates key elements of TLR7 signaling beyond endosomal recognition.
Academic Article NF-kappaB activation by the Toll-IL-1 receptor domain protein MyD88 adapter-like is regulated by caspase-1.
Academic Article Recognition of hyaluronan released in sterile injury involves a unique receptor complex dependent on Toll-like receptor 4, CD44, and MD-2.
Academic Article MyD88-dependent activation of dendritic cells and CD4(+) T lymphocytes mediates symptoms, but is not required for the immunological control of parasites during rodent malaria.
Academic Article Ligand-induced conformational changes allosterically activate Toll-like receptor 9.
Academic Article Plasmodium falciparum infection causes proinflammatory priming of human TLR responses.
Academic Article MUC1 mucin is a negative regulator of toll-like receptor signaling.
Academic Article Failure of TLR4-driven NF-kappa B activation to stimulate virus replication in models of HIV type 1 activation.
Academic Article Cathepsin K-dependent toll-like receptor 9 signaling revealed in experimental arthritis.
Academic Article Lymphocytic choriomeningitis virus (LCMV) infection of CNS glial cells results in TLR2-MyD88/Mal-dependent inflammatory responses.
Academic Article Lipoproteins are critical TLR2 activating toxins in group B streptococcal sepsis.
Academic Article Analysis of the activity to induce toll-like receptor (TLR)2- and TLR4-mediated stimulation of supragingival plaque.
Academic Article Recruitment and endo-lysosomal activation of TLR9 in dendritic cells infected with Trypanosoma cruzi.
Academic Article TLR2 and its co-receptors determine responses of macrophages and dendritic cells to lipoproteins of Mycobacterium tuberculosis.
Academic Article TAG, a splice variant of the adaptor TRAM, negatively regulates the adaptor MyD88-independent TLR4 pathway.
Academic Article MyD88 adapter-like (Mal)/TIRAP interaction with TRAF6 is critical for TLR2- and TLR4-mediated NF-kappaB proinflammatory responses.
Academic Article Alternating 2'-O-ribose methylation is a universal approach for generating non-stimulatory siRNA by acting as TLR7 antagonist.
Academic Article MD-2-mediated ionic interactions between lipid A and TLR4 are essential for receptor activation.
Academic Article TLR2 mediates recognition of live Staphylococcus epidermidis and clearance of bacteremia.
Academic Article Viral inhibitory peptide of TLR4, a peptide derived from vaccinia protein A46, specifically inhibits TLR4 by directly targeting MyD88 adaptor-like and TRIF-related adaptor molecule.
Academic Article UNC93B1 mediates host resistance to infection with Toxoplasma gondii.
Academic Article TLR3-mediated IFN-? gene induction is negatively regulated by the TLR adaptor MyD88 adaptor-like.
Academic Article Therapeutical targeting of nucleic acid-sensing Toll-like receptors prevents experimental cerebral malaria.
Academic Article Toll-like receptors participate in macrophage activation and intracellular control of Leishmania (Viannia) panamensis.
Academic Article Requirement of UNC93B1 reveals a critical role for TLR7 in host resistance to primary infection with Trypanosoma cruzi.
Academic Article Genome-wide expression profiling and mutagenesis studies reveal that lipopolysaccharide responsiveness appears to be absolutely dependent on TLR4 and MD-2 expression and is dependent upon intermolecular ionic interactions.
Academic Article Toll-like receptor (TLR) 2 mediates inflammatory responses to oligomerized RrgA pneumococcal pilus type 1 protein.
Academic Article UNC93B1 and nucleic acid-sensing Toll-like receptors mediate host resistance to infection with Leishmania major.
Academic Article Interferon-? and granulocyte/monocyte colony-stimulating factor production by natural killer cells involves different signaling pathways and the adaptor stimulator of interferon genes (STING).
Academic Article The history of Toll-like receptors - redefining innate immunity.
Concept Toll-Like Receptors
Concept Toll-Like Receptor 6
Concept Toll-Like Receptor 4
Concept Toll-Like Receptor 9
Concept Toll-Like Receptor 3
Concept Toll-Like Receptor 2
Concept Toll-Like Receptor 7
Concept Toll-Like Receptor 5
Concept Toll-Like Receptor 1
Concept Toll-Like Receptor 8
Academic Article Dual engagement of the NLRP3 and AIM2 inflammasomes by plasmodium-derived hemozoin and DNA during malaria.
Academic Article TRIF signaling is essential for TLR4-driven IgE class switching.
Academic Article Metalloproteinase-dependent TLR2 ectodomain shedding is involved in soluble toll-like receptor 2 (sTLR2) production.
Academic Article MD-2 is required for disulfide HMGB1-dependent TLR4 signaling.
Academic Article Type I Interferon Induction by Neisseria gonorrhoeae: Dual Requirement of Cyclic GMP-AMP Synthase and Toll-like Receptor 4.
Academic Article Control of the innate immune response by the mevalonate pathway.
Academic Article miR-718 represses proinflammatory cytokine production through targeting phosphatase and tensin homolog (PTEN).
Academic Article The Single Nucleotide Polymorphism Mal-D96N Mice Provide New Insights into Functionality of Mal in TLR Immune Responses.
Academic Article The TLR4 adaptor TRAM controls the phagocytosis of Gram-negative bacteria by interacting with the Rab11-family interacting protein 2.
Academic Article The immunology of Plasmodium vivax malaria.
Academic Article Human endogenous retrovirus HERV-K(HML-2) RNA causes neurodegeneration through Toll-like receptors.
Academic Article Clostridioides difficile Toxin A Remodels Membranes and Mediates DNA Entry Into Cells to Activate Toll-Like Receptor 9 Signaling.
Academic Article Caspase-8 mediates inflammation and disease in rodent malaria.
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