Although inflammation is essential for the body to protect itself against infection, when the process becomes overly aggressive it contributes to a host of inflammatory conditions including inflammatory bowel diseases, heart disease, autoimmune disorders, and sepsis. The laboratory studies the molecular mechanisms by which blood phagocytes such as macrophages and dendritic cells recognize microbial pathogens and initiate inflammatory responses.
The Underhill laboratory is focused on understanding basic mechanisms of innate immunity and control of inflammation during disease. The lab has been particularly focused on the role of phagocytosis in macrophages and dendritic cells in modulating inflammatory signaling, making important contributions to defining Toll-like receptor ligands, characterizing Toll-like receptor signaling pathways, characterizing C-type lectin signaling pathways and in defining the role of microbial degradation in triggering innate immune responses including inflammasome activation. Recently, the laboratory has described the presence of fungi in the microbiome of the gut and is actively engaged in understanding the biology of this ”mycobiome” and how it interacts with the immune system and contributes to health and disease.
Wolf Andrea J, Reyes Christopher N, Liang Wenbin, Becker Courtney, Shimada Kenichi, Wheeler Matthew L, Cho Hee Cheol, Popescu Narcis I, Coggeshall K Mark, Arditi Moshe, Underhill David M Hexokinase Is an Innate Immune Receptor for the Detection of Bacterial Peptidoglycan Cell, 2016; 166(3): 624-36.
Wheeler Matthew L, Limon Jose J, Bar Agnieszka S, Leal Christian A, Gargus Matthew, Tang Jie, Brown Jordan, Funari Vincent A, Wang Hanlin L, Crother Timothy R, Arditi Moshe, Underhill David M, Iliev Iliyan D Immunological Consequences of Intestinal Fungal Dysbiosis Cell host & microbe, 2016; 19(6): 865-73.
Underhill David M, Pearlman Eric Immune Interactions with Pathogenic and Commensal Fungi: A Two-Way Street Immunity, 2015; 43(5): 845-58.
MÃ¼ller Sabrina, Wolf Andrea J, Iliev Iliyan D, Berg Bethany L, Underhill David M, Liu George Y Poorly Cross-Linked Peptidoglycan in MRSA Due to mecA Induction Activates the Inflammasome and Exacerbates Immunopathology Cell host & microbe, 2015; 18(5): 604-12.
Tang Jie, Iliev Iliyan D, Brown Jordan, Underhill David M, Funari Vincent A Mycobiome: Approaches to analysis of intestinal fungi Journal of immunological methods, 2015; 421(5): 112-21.
Underhill David M, Iliev Iliyan D The mycobiota: interactions between commensal fungi and the host immune system Nature reviews. Immunology, 2014; 14(6): 405-16.
Ma Jun, Becker Courtney, Reyes Christopher, Underhill David M Cutting edge: FYCO1 recruitment to dectin-1 phagosomes is accelerated by light chain 3 protein and regulates phagosome maturation and reactive oxygen production Journal of immunology (Baltimore, Md. : 1950), 2014; 192(4): 1356-60.
Kaplan Amber, Ma Jun, Kyme Pierre, Wolf Andrea J, Becker Courtney A, Tseng Ching Wen, Liu George Y, Underhill David M Failure to induce IFN-Î² production during Staphylococcus aureus infection contributes to pathogenicity Journal of immunology (Baltimore, Md. : 1950), 2012; 189(9): 4537-45.
Ma Jun, Becker Courtney, Lowell Clifford A, Underhill David M Dectin-1-triggered recruitment of light chain 3 protein to phagosomes facilitates major histocompatibility complex class II presentation of fungal-derived antigens The Journal of biological chemistry, 2012; 287(41): 34149-56.
Goodridge Helen S, Underhill David M, Touret Nicolas Mechanisms of Fc receptor and dectin-1 activation for phagocytosis Traffic (Copenhagen, Denmark), 2012; 13(8): 1062-71.
Underhill David M, Goodridge Helen S Information processing during phagocytosis Nature reviews. Immunology, 2012; 12(7): 492-502.
Iliev Iliyan D, Funari Vincent A, Taylor Kent D, Nguyen Quoclinh, Reyes Christopher N, Strom Samuel P, Brown Jordan, Becker Courtney A, Fleshner Phillip R, Dubinsky Marla, Rotter Jerome I, Wang Hanlin L, McGovern Dermot P B, Brown Gordon D, Underhill David M Interactions between commensal fungi and the C-type lectin receptor Dectin-1 influence colitis Science (New York, N.Y.), 2012; 336(6086): 1314-7.
Shimada Kenichi, Crother Timothy R, Karlin Justin, Dagvadorj Jargalsaikhan, Chiba Norika, Chen Shuang, Ramanujan V Krishnan, Wolf Andrea J, Vergnes Laurent, Ojcius David M, Rentsendorj Altan, Vargas Mario, Guerrero Candace, Wang Yinsheng, Fitzgerald Katherine A, Underhill David M, Town Terrence, Arditi Moshe Oxidized mitochondrial DNA activates the NLRP3 inflammasome during apoptosis Immunity, 2012; 36(3): 401-14.
Wolf Andrea J, Arruda Andrea, Reyes Christopher N, Kaplan Amber T, Shimada Takahiro, Shimada Kenichi, Arditi Moshe, Liu George, Underhill David M Phagosomal degradation increases TLR access to bacterial ligands and enhances macrophage sensitivity to bacteria Journal of immunology (Baltimore, Md. : 1950), 2011; 187(11): 6002-10.
Goodridge Helen S, Reyes Christopher N, Becker Courtney A, Katsumoto Tamiko R, Ma Jun, Wolf Andrea J, Bose Nandita, Chan Anissa S H, Magee Andrew S, Danielson Michael E, Weiss Arthur, Vasilakos John P, Underhill David M Activation of the innate immune receptor Dectin-1 upon formation of a 'phagocytic synapse' Nature, 2011; 472(7344): 471-5.
Shimada Takahiro, Park Bong Goo, Wolf Andrea J, Brikos Constantinos, Goodridge Helen S, Becker Courtney A, Reyes Christopher N, Miao Edward A, Aderem Alan, GÃ¶tz Friedrich, Liu George Y, Underhill David M Staphylococcus aureus evades lysozyme-based peptidoglycan digestion that links phagocytosis, inflammasome activation, and IL-1beta secretion Cell host & microbe, 2010; 7(1): 38-49.
Goodridge Helen S, Shimada Takahiro, Wolf Andrea J, Hsu Yen-Michael S, Becker Courtney A, Lin Xin, Underhill David M Differential use of CARD9 by dectin-1 in macrophages and dendritic cells Journal of immunology (Baltimore, Md. : 1950), 2009; 182(2): 1146-54.
Underhill David M, Rossnagle Eddie, Lowell Clifford A, Simmons Randi M Dectin-1 activates Syk tyrosine kinase in a dynamic subset of macrophages for reactive oxygen production Blood, 2005; 106(7): 2543-50.
Gantner Benjamin N, Simmons Randi M, Canavera Scott J, Akira Shizuo, Underhill David M Collaborative induction of inflammatory responses by dectin-1 and Toll-like receptor 2 The Journal of experimental medicine, 2003; 197(9): 1107-17.
Underhill David M, Ozinsky Adrian Phagocytosis of microbes: complexity in action Annual review of immunology, 2002; 20(1): 825-52.
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