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Felix O. Yarovinsky, M.D.

Felix O. Yarovinsky, M.D.

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Yarovinsky Lab

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About Me

Faculty Appointments

Professor - Department of Microbiology and Immunology (SMD)

Research

The goal of my laboratory is to understand the cellular and molecular mechanisms that account for host resistance to protozoan parasites. We seek to decipher how innate immune cells cooperate in the regulation of IFN-gamma responses to the infection.

Expertise within my laboratory includes: ...
The goal of my laboratory is to understand the cellular and molecular mechanisms that account for host resistance to protozoan parasites. We seek to decipher how innate immune cells cooperate in the regulation of IFN-gamma responses to the infection.

Expertise within my laboratory includes: innate immune cell biology, Toll-like receptors, mouse models of innate immune deficiencies, and the regulation of inflammatory responses by the innate immune system.

Our approach has been multidisciplinary, ranging from the creation of new mouse models with altered innate immune functions, to detailed biochemical and structural analyses of TLRs involved in recognition of protozoan parasites. The innovative use of cell type-specific ablation of the TLR/IL-1R adaptor protein MyD88 using the Cre-lox system has allowed us to dissect the mechanism by which innate immune cell collaborate to kill Toxoplasma organisms and to restrict their expansion, which is necessary to achieve protection from infection (PNAS, 2011; Nature Immunology, 2013). In a paper published in The Journal of Biological Chemistry in 2011 we established that TLR11, a protozoan protein sensor, has an intracellular localization that is controlled by a chaperone protein, Unc93B1. More recently (PNAS, 2013; Infection & Immunity, 2014; JI, 2015), we revealed that IFN-gamma can be produced by neutrophils. This is a major finding since neutrophils are the most numerous immune cell type. Our results revealed a new arm in innate immunity that addresses many basic and medically important questions in the field.

Our recent studies comparing T. gondii infected gnotobiotic (germ-free) animals to conventional mice have established that the immunostimulatory signals induced by commensal bacteria have major effects on the outcomes of the parasitic infections (Cell Host & Microbe, 2009, Nature Immunology, 2013). We are particular interested in understanding how the intestinal microbiota regulates host defense, tissue immunity and inflammation.

Publications

Journal Articles

IFN-? mediates Paneth cell death via suppression of mTOR.

Araujo A, Safronova A, Burger E, López-Yglesias A, Giri S, Camanzo ET, Martin AT, Grivennikov S, Yarovinsky F

eLife.. 2021 October 1110 Epub 10/11/2021.

T-bet-dependent ILC1- and NK cell-derived IFN-? mediates cDC1-dependent host resistance against Toxoplasma gondii.

López-Yglesias AH, Burger E, Camanzo E, Martin AT, Araujo AM, Kwok SF, Yarovinsky F

PLoS pathogens.. 2021 January 1917 (1):e1008299. Epub 01/19/2021.

Immediate interferon gamma induction determines murine host compatibility differences between and .

Coombs RS, Blank ML, English ED, Adomako-Ankomah Y, Urama IS, Martin AT, Yarovinsky F, Boyle JP

Infection and immunity.. 2020 February 3 Epub 02/03/2020.

TLR11-independent inflammasome activation is critical for CD4+ T cell-derived IFN-? production and host resistance to Toxoplasma gondii.

López-Yglesias AH, Camanzo E, Martin AT, Araujo AM, Yarovinsky F

PLoS pathogens.. 2019 June 15 (6):e1007872. Epub 06/13/2019.

Alarmin S100A11 initiates a chemokine response to the human pathogen Toxoplasma gondii.

Safronova A, Araujo A, Camanzo ET, Moon TJ, Elliott MR, Beiting DP, Yarovinsky F

Nature immunology.. 2018 November 19 Epub 11/19/2018.

T-bet-independent Th1 response induces intestinal immunopathology during Toxoplasma gondii infection.

López-Yglesias AH, Burger E, Araujo A, Martin AT, Yarovinsky F

Mucosal immunology.. 2018 May 11 (3):921-931. Epub 01/03/2018.

Loss of Paneth Cell Autophagy Causes Acute Susceptibility to Toxoplasma gondii-Mediated Inflammation.

Burger E, Araujo A, López-Yglesias A, Rajala MW, Geng L, Levine B, Hooper LV, Burstein E, Yarovinsky F

Cell host & microbe.. 2018 February 1423 (2):177-190.e4. Epub 01/18/2018.

Loss of Paneth Cell Autophagy Causes Acute Susceptibility to Toxoplasma gondii-Mediated Inflammation

Burger, E; Araujo, A; López-Yglesias, A; Rajala, MW; Geng, L; Levine, B; Hooper, LV; Burstein, E; Yarovinsky, F.

Cell Host & Microbe. 2018; .

Absence of TLR11 in Mice Does Not Confer Susceptibility to Salmonella Typhi.

Song J, Wilhelm CL, Wangdi T, Maira-Litran T, Lee SJ, Raetz M, Sturge CR, Mirpuri J, Pei J, Grishin NV, McSorley SJ, Gewirtz AT, Bäumler AJ, Pier GB, Galán JE, Yarovinsky F

Cell.. 2016 February 25164 (5):827-8. Epub 1900 01 01.

Cutting Edge: Developmental Regulation of IFN-? Production by Mouse Neutrophil Precursor Cells.

Sturge CR, Burger E, Raetz M, Hooper LV, Yarovinsky F

The Journal of immunology : official journal of the American Association of Immunologists.. 2015 July 1195 (1):36-40. Epub 05/29/2015.

TLR5-mediated sensing of gut microbiota is necessary for antibody responses to seasonal influenza vaccination.

Oh JZ, Ravindran R, Chassaing B, Carvalho FA, Maddur MS, Bower M, Hakimpour P, Gill KP, Nakaya HI, Yarovinsky F, Sartor RB, Gewirtz AT, Pulendran B

Immunity.. 2014 September 1841 (3):478-492. Epub 09/11/2014.

Apicomplexan infections in the gut.

Wilhelm CL, Yarovinsky F

Parasite immunology.. 2014 September 36 (9):409-20. Epub 1900 01 01.

Complex immune cell interplay in the gamma interferon response during Toxoplasma gondii infection.

Sturge CR, Yarovinsky F

Infection and immunity.. 2014 August 82 (8):3090-7. Epub 05/27/2014.

Copper metabolism domain-containing 1 represses genes that promote inflammation and protects mice from colitis and colitis-associated cancer.

Li H, Chan L, Bartuzi P, Melton SD, Weber A, Ben-Shlomo S, Varol C, Raetz M, Mao X, Starokadomskyy P, van Sommeren S, Mokadem M, Schneider H, Weisberg R, Westra HJ, Esko T, Metspalu A, Kumar V, Faubion WA, Yarovinsky F, Hofker M, Wijmenga C, Kracht M, Franke L, Aguirre V, Weersma RK, Gluck N, van de Sluis B, Burstein E

Gastroenterology.. 2014 July 147 (1):184-195.e3. Epub 04/13/2014.

Innate immunity to Toxoplasma gondii infection.

Yarovinsky F

Nature reviews. Immunology.. 2014 February 14 (2):109-21. Epub 1900 01 01.

Proteobacteria-specific IgA regulates maturation of the intestinal microbiota.

Mirpuri J, Raetz M, Sturge CR, Wilhelm CL, Benson A, Savani RC, Hooper LV, Yarovinsky F

Gut microbes.. 2014 5 (1):28-39. Epub 09/25/2013.

Cooperation of TLR12 and TLR11 in the IRF8-dependent IL-12 response to Toxoplasma gondii profilin.

Raetz M, Kibardin A, Sturge CR, Pifer R, Li H, Burstein E, Ozato K, Larin S, Yarovinsky F

The Journal of immunology : official journal of the American Association of Immunologists.. 2013 November 1191 (9):4818-27. Epub 09/27/2013.

TLR-independent neutrophil-derived IFN-? is important for host resistance to intracellular pathogens.

Sturge CR, Benson A, Raetz M, Wilhelm CL, Mirpuri J, Vitetta ES, Yarovinsky F

Proceedings of the National Academy of Sciences of the United States of America.. 2013 June 25110 (26):10711-6. Epub 06/10/2013.

Parasite-induced TH1 cells and intestinal dysbiosis cooperate in IFN-?-dependent elimination of Paneth cells.

Raetz M, Hwang SH, Wilhelm CL, Kirkland D, Benson A, Sturge CR, Mirpuri J, Vaishnava S, Hou B, Defranco AL, Gilpin CJ, Hooper LV, Yarovinsky F

Nature immunology.. 2013 February 14 (2):136-42. Epub 12/23/2012.

B cell TLR7 expression drives anti-RNA autoantibody production and exacerbates disease in systemic lupus erythematosus-prone mice.

Hwang SH, Lee H, Yamamoto M, Jones LA, Dayalan J, Hopkins R, Zhou XJ, Yarovinsky F, Connolly JE, Curotto de Lafaille MA, Wakeland EK, Fairhurst AM

The Journal of immunology : official journal of the American Association of Immunologists.. 2012 December 15189 (12):5786-96. Epub 11/12/2012.

Adenoma-linked barrier defects and microbial products drive IL-23/IL-17-mediated tumour growth.

Grivennikov SI, Wang K, Mucida D, Stewart CA, Schnabl B, Jauch D, Taniguchi K, Yu GY, Osterreicher CH, Hung KE, Datz C, Feng Y, Fearon ER, Oukka M, Tessarollo L, Coppola V, Yarovinsky F, Cheroutre H, Eckmann L, Trinchieri G, Karin M

Nature.. 2012 November 8491 (7423):254-8. Epub 1900 01 01.

B cell-intrinsic MyD88 signaling prevents the lethal dissemination of commensal bacteria during colonic damage.

Kirkland D, Benson A, Mirpuri J, Pifer R, Hou B, DeFranco AL, Yarovinsky F

Immunity.. 2012 February 2436 (2):228-38. Epub 02/01/2012.

Microbial infection-induced expansion of effector T cells overcomes the suppressive effects of regulatory T cells via an IL-2 deprivation mechanism.

Benson A, Murray S, Divakar P, Burnaevskiy N, Pifer R, Forman J, Yarovinsky F

The Journal of immunology : official journal of the American Association of Immunologists.. 2012 January 15188 (2):800-10. Epub 12/05/2011.

IL-6 signaling SOCS critical for IL-12 host response to Toxoplasma gondii.

Mirpuri J, Yarovinsky F

Future microbiology.. 2012 January 7 (1):13-6. Epub 1900 01 01.

Therapeutic helminth infection of macaques with idiopathic chronic diarrhea alters the inflammatory signature and mucosal microbiota of the colon.

Broadhurst MJ, Ardeshir A, Kanwar B, Mirpuri J, Gundra UM, Leung JM, Wiens KE, Vujkovic-Cvijin I, Kim CC, Yarovinsky F, Lerche NW, McCune JM, Loke P

PLoS pathogens.. 2012 8 (11):e1003000. Epub 11/15/2012.

Lactobacillus rhamnosus (LGG) regulates IL-10 signaling in the developing murine colon through upregulation of the IL-10R2 receptor subunit.

Mirpuri J, Sotnikov I, Myers L, Denning TL, Yarovinsky F, Parkos CA, Denning PW, Louis NA

PloS one.. 2012 7 (12):e51955. Epub 12/18/2012.

Norovirus regulation of the innate immune response and apoptosis occurs via the product of the alternative open reading frame 4.

McFadden N, Bailey D, Carrara G, Benson A, Chaudhry Y, Shortland A, Heeney J, Yarovinsky F, Simmonds P, Macdonald A, Goodfellow I

PLoS pathogens.. 2011 December 7 (12):e1002413. Epub 12/08/2011.

Innate responses to Toxoplasma gondii in mice and humans.

Pifer R, Yarovinsky F

Trends in parasitology.. 2011 September 27 (9):388-93. Epub 1900 01 01.

Toxoplasma gondii rhoptry kinase ROP16 activates STAT3 and STAT6 resulting in cytokine inhibition and arginase-1-dependent growth control.

Butcher BA, Fox BA, Rommereim LM, Kim SG, Maurer KJ, Yarovinsky F, Herbert DR, Bzik DJ, Denkers EY

PLoS pathogens.. 2011 September 7 (9):e1002236. Epub 09/08/2011.

Gammadelta intraepithelial lymphocytes are essential mediators of host-microbial homeostasis at the intestinal mucosal surface.

Ismail AS, Severson KM, Vaishnava S, Behrendt CL, Yu X, Benjamin JL, Ruhn KA, Hou B, DeFranco AL, Yarovinsky F, Hooper LV

Proceedings of the National Academy of Sciences of the United States of America.. 2011 May 24108 (21):8743-8. Epub 05/09/2011.

UNC93B1 is essential for TLR11 activation and IL-12-dependent host resistance to Toxoplasma gondii.

Pifer R, Benson A, Sturge CR, Yarovinsky F

The Journal of biological chemistry.. 2011 February 4286 (5):3307-14. Epub 11/19/2010.

Critical coordination of innate immune defense against Toxoplasma gondii by dendritic cells responding via their Toll-like receptors.

Hou B, Benson A, Kuzmich L, DeFranco AL, Yarovinsky F

Proceedings of the National Academy of Sciences of the United States of America.. 2011 January 4108 (1):278-83. Epub 12/20/2010.

Invariant NKT cell development requires a full complement of functional CD3 zeta immunoreceptor tyrosine-based activation motifs.

Becker AM, Blevins JS, Tomson FL, Eitson JL, Medeiros JJ, Yarovinsky F, Norgard MV, van Oers NS

The Journal of immunology : official journal of the American Association of Immunologists.. 2010 June 15184 (12):6822-32. Epub 05/14/2010.

Redundant and pathogenic roles for IL-22 in mycobacterial, protozoan, and helminth infections.

Wilson MS, Feng CG, Barber DL, Yarovinsky F, Cheever AW, Sher A, Grigg M, Collins M, Fouser L, Wynn TA

The Journal of immunology : official journal of the American Association of Immunologists.. 2010 April 15184 (8):4378-90. Epub 03/10/2010.

Functional analysis of RNA structures present at the 3' extremity of the murine norovirus genome: the variable polypyrimidine tract plays a role in viral virulence.

Bailey D, Karakasiliotis I, Vashist S, Chung LM, Rees J, Reese J, McFadden N, Benson A, Yarovinsky F, Simmonds P, Goodfellow I

Journal of virology.. 2010 March 84 (6):2859-70. Epub 01/06/2010.

Toxoplasma gondii inhibits R5 HIV-1 replication in human lymphoid tissues ex vivo.

Sassi A, Brichacek B, Hieny S, Yarovinsky F, Golding H, Grivel JC, Sher A, Margolis L

Microbes and infection. 2009 December 11 (14-15):1106-13. Epub 08/09/2009.

Gut commensal bacteria direct a protective immune response against Toxoplasma gondii.

Benson A, Pifer R, Behrendt CL, Hooper LV, Yarovinsky F

Cell host & microbe.. 2009 August 206 (2):187-96. Epub 1900 01 01.

Induction of adaptive immunity by flagellin does not require robust activation of innate immunity.

Sanders CJ, Franchi L, Yarovinsky F, Uematsu S, Akira S, Núñez G, Gewirtz AT

European journal of immunology.. 2009 February 39 (2):359-71. Epub 1900 01 01.

Recognition of Toxoplasma gondii by TLR11 prevents parasite-induced immunopathology.

Yarovinsky F, Hieny S, Sher A

The Journal of immunology : official journal of the American Association of Immunologists.. 2008 December 15181 (12):8478-84. Epub 1900 01 01.

Toll-like receptors and their role in host resistance to Toxoplasma gondii.

Yarovinsky F

Immunology letters.. 2008 August 15119 (1-2):17-21. Epub 06/18/2008.

Plasmacytoid dendritic cells are activated by Toxoplasma gondii to present antigen and produce cytokines.

Pepper M, Dzierszinski F, Wilson E, Tait E, Fang Q, Yarovinsky F, Laufer TM, Roos D, Hunter CA

The Journal of immunology : official journal of the American Association of Immunologists.. 2008 May 1180 (9):6229-36. Epub 1900 01 01.

Toxoplasma profilin is essential for host cell invasion and TLR11-dependent induction of an interleukin-12 response.

Plattner F, Yarovinsky F, Romero S, Didry D, Carlier MF, Sher A, Soldati-Favre D

Cell host & microbe.. 2008 February 143 (2):77-87. Epub 1900 01 01.

Toll-like receptor recognition regulates immunodominance in an antimicrobial CD4+ T cell response.

Yarovinsky F, Kanzler H, Hieny S, Coffman RL, Sher A

Immunity.. 2006 October 25 (4):655-64. Epub 09/28/2006.

Toll-like receptor recognition of Toxoplasma gondii.

Yarovinsky F, Sher A

International journal for parasitology.. 2006 March 36 (3):255-9. Epub 01/13/2006.

CCR5 N-terminal region plays a critical role in HIV-1 inhibition by Toxoplasma gondii-derived cyclophilin-18.

Golding H, Khurana S, Yarovinsky F, King LR, Abdoulaeva G, Antonsson L, Owman C, Platt EJ, Kabat D, Andersen JF, Sher A

The Journal of biological chemistry.. 2005 August 19280 (33):29570-7. Epub 06/23/2005.

TLR11 activation of dendritic cells by a protozoan profilin-like protein.

Yarovinsky F, Zhang D, Andersen JF, Bannenberg GL, Serhan CN, Hayden MS, Hieny S, Sutterwala FS, Flavell RA, Ghosh S, Sher A

Science.. 2005 June 10308 (5728):1626-9. Epub 04/28/2005.

Mouse cathelin-related antimicrobial peptide chemoattracts leukocytes using formyl peptide receptor-like 1/mouse formyl peptide receptor-like 2 as the receptor and acts as an immune adjuvant.

Kurosaka K, Chen Q, Yarovinsky F, Oppenheim JJ, Yang D

The Journal of immunology : official journal of the American Association of Immunologists.. 2005 May 15174 (10):6257-65. Epub 1900 01 01.

Structural determinants of the anti-HIV activity of a CCR5 antagonist derived from Toxoplasma gondii.

Yarovinsky F, Andersen JF, King LR, Caspar P, Aliberti J, Golding H, Sher A

The Journal of biological chemistry.. 2004 December 17279 (51):53635-42. Epub 10/06/2004.

Distinct contributions of TNF and LT cytokines to the development of dendritic cells in vitro and their recruitment in vivo.

Abe K, Yarovinsky FO, Murakami T, Shakhov AN, Tumanov AV, Ito D, Drutskaya LN, Pfeffer K, Kuprash DV, Komschlies KL, Nedospasov SA

Blood.. 2003 February 15101 (4):1477-83. Epub 1900 01 01.

Cyclosporin A blocks the expression of lymphotoxin alpha, but not lymphotoxin beta, in human peripheral blood mononuclear cells.

Kuprash DV, Boitchenko VE, Yarovinsky FO, Rice NR, Nordheim A, Rühlmann A, Nedospasov SA

Blood.. 2002 September 1100 (5):1721-7. Epub 1900 01 01.

Obtaining of monoclonal antibodies by means of DNA immunization.

Surovoi AY, Sukhacheva EA, Wert MY, Yarovinsky FO, Zeinalova ES, Gaunitz F, Uberahm E, Gebhardt R

Doklady. Biochemistry and biophysics.. 2001 379 :255-6. Epub 1900 01 01.