RESEARCH
SUMMARY
Research in this
laboratory is directed at understanding
the cellular and cytokine mechanisms regulating
immune defenses. We are particularly interested
in the responses to acute viral infections
and links between innate and adaptive immunity.
Basic pathways regulating natural killer
(NK) and T cells are being defined. Studies
of the expression and function of a number
of cytokines, including the type 1 interferons
(IFN-
a/ß), IFN-g, interleukin 12 (IL-12),
IL-18, and tumor necrosis factor (TNF),
are being carried out.
The intracellular biochemical signaling
pathways promoting their effects in the
context of endogenous responses, particularly
the role for the signal transducers and
activators of transcription (STATs), are
being elucidated. To characterize the mechanisms
for stress and environmental effects on
health, our work is identifying interactions
between the neuroendocrine and immune systems.
The results have implications for understanding
the balance between protective and detrimental
immune responses, and the rational design
of therapeutic interventions for defense
against infections.
back to top
REPRESENTATIVE PUBLICATIONS
Gil, M.P., R. Salomon, J. Louten, and C.A. Biron. Modulation of STAT1 protein levels, a
mechanism shaping CD8 T cell responses in vivo. Blood 107:987-993, 2006.
Paper Featured in Issue Comment
Huang, D.R., F.-D. Shi, s. Jung, G.C. Pien, J. Wang, T.P. Salazar-Mather, T.T. He, J.T.
Weaver, H.-G. Ljunggren, C.A. Biron, D.R. Littman, R.M. Ransohoff. The neuronal
chemokine CX3CL1/fractalkin selectively recruits NK cells that modify experimental
autoimmne encephalomyletis within the central nervous system. FASEB J. 20:896-905,
2006.
Garcia-Sastre, A., and C.A. Biron. Type 1 interferons and the virus-host relation-
ship: A lesson in deténte. Science 312:879-882, 2006. Invited Review for Special Issue
Sjölin, H., S.H. Robbins, G. Bessou, Å. Hidmark, E. Tomasello, M. Johansson. H. Hall, F.
Charifi, G.B. Karlsson Hedestam, C.A. Biron, K. Kärre, P. Höglund, E. Vivier, and M. Dalod.
DAP12 signaling regulates palasmacytoid dendritic cell homeostasis and down-modulates their
function during infection. J. Immunol. 177:2908-2916, 2006.
Louten, J., N. van Rooijen, and C.A. Biron. Type 1 interferon deficiency in the absence of
normal splenic architecture during lymphocytic choriomeningitis virus infection.
J. Immunol. 177:3266-3272, 2006. Paper Featured "In This Issue" Section
Hokeness, K.L., W.A. Kuziel, C.A. Biron, and T.P. Salazar-Mather. Monocyte
chemoattractant protein-1 (MCP-1) and CCR2 interactions are required for IFN-±D≤-
induced inflammatory responses and antiviral defense in liver. J. Immunol. 174:1549-
1556, 2005.
Morra, M., R.A. Barrington, A.C. Abadia-Molina, S. Okamoto, A. Julien, C. Gullo, A. Kalsey,
M.J. Edwards, G. Chen, R. Spolski, W.J. Leonard, B.T. Huber, P. Borrow, C.A. Biron, A.R.
Satoskar, M.C. Carroll, and C. Terhorst. Defective B cell responses in the absence of SH2D1A.
Proc. Natl. Acad. Sci. USA 102:4819-4823, 2005.
Silverman, M.N., B.D. Pearce, C.A. Biron, and A.H. Miller. Immune modulation of the
hypothalamic-pituitary-adrenal (HPA) axis during viral infection. Viral Immunol. 18:41-
78, 2005. Invited Review
Delale, T., A. Paquin, C. Asselin-Paturel, M. Dalod, G. Brizard, E.E. Bates, P. Ksastner, S.
Chan, S. Akira, A. Vicari, C.A. Biron, G. Trinchieri, and F. Brière. MyD88-dependent and
-independent murine cytomegalovirus sensing for IFN-± release and initiation of immune
responses in vivo. J. Immunol. 175:6723-6732, 2005.
Silverman, M.N., A.H. Miller, C.A. Biron, and B.D. Pearce. Characterization of an IL-6 and
ACTH dependent, immune to adrenal pathway during viral infections. Endocrinology
145:3580-3589, 2004. Paper Featured in Editorial Review
Townsend, M., A.S. Weinmann, J. Matsuda, R. Salomon, P. Farnham, C.A.Biron, L. Gapin, and L.H. Glimcher. T-bet regulates the terminal maturation and homeostasis of NK and Va14iNKT cells. Immunity 20:477-494,2004. Paper Featured in Issue Preview
Serbina, N.V., T.P. Salazar-Mather, C.A.Biron, W.A. Kuziel, and E.G. Pamer. TNF/iNOS producing dendritic cells (Tip-DC) mediate innate immune defense against bacterial infection. Immunity 19:59-70, 2003. Paper Featured in Issue Preview
Durbin, J., L. Doughty, K. Nguyen, M. Caliguri, J. Van Deusen, and C.Biron. The role of STAT1 in viral sensitization to LPS. J. Endotoxin Res.9:313-6, 2003.
Dalod, M., T. Hamilton, R. Salomon, T.P. Salazar-Mather, S. Henry, J.D. Hamilton, and C.A.Biron. Dendritic cell responses to early murine cytomegalovirus interfection: subset functional specialization and differential regulation by interferon alpha/beta. J. Exp. Med. 197:885-898, 2003.
Biron,C.A., R. Salomon, and J.E. Durbin. Stats in Immune Responses to Viral Infections. In: Signal Transducers and Activators of Transcription (STATs). P.B. Segal, D.E. Levy, and T. Hirano, eds., Kluwer Academic Publishers, p. 381-397, 2003.
Vivier, E. and C.A.Biron. A pathogen receptor on natural killer cells. Science296:1248-1249, 2002. Invited Perspective
Salazar-Mather, T.P., C.A. Lewis, and C.A.Biron. Type I interferons regulate inflammatory cell trafficking and macrophage inflammatory protein-1a delivery to liver. J. Clin. Invest. 110:321-330, 2002.
Kelsall, B.L., C.A.Biron, O. Sharma, and P.M. Kaye. Dendritic cells at the host-pathogen interface. Nature Immunol.3:699-702, 2002. Invited Meeting Report
Nguyen, K.B., W.T. Watford, R. Salomon, S.R. Hofmann, G.C. Pien, A. Morinobu, M. Gadina, J.J. O'Shea, and C.A.Biron. Critical role for STAT4 activation by type 1 interferons in the interferon-g response to viral infection. Science297:2063-2066, 2002.
Nguyen, K.B., T.P. Salazar-Mather, M.Y. Dalod, J.B. Van Deusen, X.-q. Wei, F.Y. Liew, M.A. Caligiuri, J.E. Durbin and C.A.Biron. Coordinated and distinct roles for IFN-a/b, IL-12, and IL-15 regulation of NK cell responses to viral infections. J. Immunol.169:4279-4287, 2002.
Pien, G.C., K.B. Nguyen, L. Malmgaard, A.R. Satoskar, and C.A.Biron. A unique mechanism for innate cytokine promotion of T cell responses to viral infections. J. Immunol. 169:5827-5837, 2002.
Biron, C.A.,
K. Nguyen, and G. Pien. Innate Immune Responses
to LCMV Infections: Natural Killer Cells
and Cytokines. In: Current
Topics in Microbiology and Immunology -
Volume 263, Arenaviruses II; Biology and
Pathogenesis. M.B.A. Oldstone, ed., Springer-Verlag,
p. 7-27, 2002.
Biron, C.A. Interferon
a and b as an immune regulators - a new look. Immunity 14:661-664,
2001.
Biron, C.A., M. Dalod,
and T.P. Salazar-Mather. Innate Immunity
and Viral Infections. In: Immunity to Infections.
S.H.E. Kaufmann, A. Sherr, and R. Ahmed,
eds., American Society for Microbiology,
p.139-160, 2001.
Biron, C.A., and L. Brossay.
NK and NK T cells in innate defense against
viral infections. Curr.
Opin. Immunol. 13:458-464, 2001.
Miller, A.H., B.D. Pearce, M.C. Ruzek, and
C.A Biron. Interactions
between the hypothalamic-pituitary-adrenal
axis and immune system during viral infection:
pathways for environmental effects on disease
expression. In: Handbook of Physiology,
Section 7, The Endocrine System, Volume
IV: Coping with the Environment - Neural
and Endocrine Mechanisms. B. S. McEwen,
ed., Oxford Press, New York, NY, p. 425-450,
2001.
Pearce B.D., C.A. Biron,
and A.H. Miller. Neuroendocrine-immune interactions
during viral infections. In: Neuroviology,
Advances in Virus Research, Vol. 56. M Buchmeier
and I. Campbell, eds., Academic Press, New
York, NY, p. 469-513, 2001.
Biron, C.A., and G.C. Sen.
Interferons and Other Cytokines. In: Fields
Virology, Fourth Edition and Fundamental
Virology, Fourth Edition. D.M. Knipe, P.M.
Howley, D.E. Griffin, R.A. Lamb, M.A. Martin,
B. Roizman, and S.E. Straus, eds., Lippincott,
Williams & Wilkins, p. 321-351, 2001.
Karp,
C.L., C.A. Biron, and D.N. Irani. Interferon-b
in multiple sclerosis: is IL-12 suppression
the key? Immunology Today 21:24-28, 2000.
Biron, C.A. Initial and
innate responses to virus infection - pattern
setting in immunity or disease. Curr. Opin. Microbiol. 2:374-381, 1999.
Biron, C.A., K.B. Nguyen,
G.C. Pien, L.P. Cousens, and T.P. Salazar-Mather.
Natural killer cells in antiviral defense:
function and regulation by innate cytokines.
Ann. Rev. Immunol.17:189-220, 1999.
Ahmed, R,. and C.A. Biron.
Immunity to viruses. In: Fundamental
Immunology, Fourth Edition, W.E. Paul,
ed., Lippincott-Raven Publishers, New York,
NY, p. 1295-1334, 1998.
Biron, C.A. Role of early cytokines, including
alpha and beta interferons (IFN-a/b),
in innate and adaptive immune responses
to viral infections. Seminars in Immunology 10:383-390, 1998.
McEwen, B.S., C.A. Biron,
K.W. Brunson, K. Bulloch, W.H. Chambers,
F.S. Dhabhar, R.H. Goldfarb, R.P. Kitson,
A.H. Miller, R.L. Spencer, and J.M. Weiss.
The role of adrenocorticoids as modulators
of immune function in health and disease:
neural, endocrine and immune interactions.
Brain Research Reviews 23:79-133, 1997.
Dalod, M., T.P. Salazar-Mather,
L. Malmgaard, C. Lewis, C. Asselin-Paturel,
F. Brière, G.Trinchieri and C.A. Biron.
IFN-a/b and IL-12
responses to viral infections: pathways
regulating dendritic cell cytokine expression
in vivo. J. Exp. Med. 195:517-528,
2002.
Malmgaard, L., T.P. Salazar-Mather, C.A.
Lewis, and C.A. Biron. Promotion of alpha/beta interferon induction
during in vivo viral infections through
alpha/beta interferon receptor/Stat1 system-dependent
and -independent pathways. J.
Virol. 76:4520-4525, 2002.
Robbins, S.H., K.B. Nguyen, N. Takahashi,
T. Mikamyama, C.A. Biron, and L. Brossay. Inhibitory functions of
the killer cell lectin-like receptor G1
molecule during the activation of mouse
NK cells. J. Immunol. 168:2585-2589,
2002. Cutting Edge Report
Asselin-Paturel, C., A. Boonstra, M. Dalod,
I. Durand, N. Yessaad, C. Dezutter-Dambuyant,
A. Vicari, A. O'Garra, C. Biron,
F. Brière, and G. Trinchieri. Mouse
type I interferon producing cells are immature
antigen-presenting cells with plasmacytoid
morphology. Provisionally accepted for publication
in Nature
Immunology 2:1144-1150, 2001.
Doughty, L.A., K.B. Nguyen, J.E. Durbin,
and C.A. Biron. A role
for IFN-a/b in
virus infection-induced sensitization to
endotoxin. J.
Immunol. 166:2658-2664, 2001.
Su, H.C., K.B. Nguyen, T.P. Salazar-Mather,
M.C. Ruzek, M.Y. Dalod, and C.A.
Biron. NK cell functions restrain
T cell responses during viral infections.
Eur.
J. Immunol. 31:3048-3055, 2001.
Wu, C., K.B. Nguyen, G.C. Pien, N. Wang,
C. Gullo, D. Howie, M.R. Sosa, M.J. Edwards,
P. Borrows, A.R. Satoskar, A.H. Sharpe,
C.A. Biron, and C. Terhorst.
SAP controls T cell responses to virus and
terminal differentiation of TH2 cells.
Nature
Immunology 2:410-414, 2001.
Nguyen, K.B., L.P. Cousens, L.A. Doughty,
G.C. Pien, J.E. Durbin, and C.A.
Biron. IFN-a/b-mediated
inhibition and promotion of IFN-g:
STAT1 resolves a paradox. Nature
Immunology 1:70-76, 2000.
Pien, G.C., and C.A. Biron. Compartmental differences in NK cell responsiveness
to IL-12 during lymphocytic choriomeningitis
virus (LCMV) infections. J. Immunol. 164:994-1001,
2000.
Pien, G.C., A.R. Satoskar, K. Takeda, S.
Akira, and C.A. Biron.
Selective IL-18 requirements for induction
of compartmental IFN-g responses during viral infection. J. Immunol. 165:4787-4791,
2000. Cutting Edge Report
Ryman, K.D., W.B. Klimstra,
K.B. Nguyen, C.A. Biron,
and R.E. Johnston. Alpha/beta interferon
protects adult mice from fatal Sindbis virus
infection and is an important determinant
of cell and tissue tropism. J.
Virol. 74:3366-3378, 2000.
Salazar-Mather, T.P., T.A. Hamilton, and
C.A. Biron. A chemokine-to-cytokine-to-chemokine
cascade critical in antiviral defense.
J. Clin. Invest. 105:985-993,
2000.
Sayós, J., K.B. Nguyen, C. Wu, S.E.
Stepp, D. Howie, J.D. Schatzle, V. Kumar,
C.A. Biron, and C. Terhorst. Potential
pathways for regulation of NK and T cell
responses: differential X-linked lymphoproliferative
syndrome gene product SAP interactions with
SLAM and 2B4. Intl. Immunol. 12:1749-1757, 2000.
Taylor, G.A., C.M. Collazo-Custodio, G.S.
Yap, K.B. Nguyen, T.A. Gregorio, L.S. Taylor,
B. Eagleson, L. Secrest, E.A. Southen, S.W.
Reid, L. Tessarollo, M. Bray, D.W. McVicar,
K. Komsclies-McConville, H.A. Young, C.A.
Biron, A. Sher, and G.F. Vande
Woude. Pathogen specific loss of host resistance
in mice lacking the interferon-g-inducible gene IGTP. Proc. Natl. Acad. Sci. USA
97:751-755, 2000.
Cousens, L.P., R. Peterson, S. Hsu, A. Dorner,
J.D. Altman, R. Ahmed, and C.A.
Biron. Two roads diverged: IFN-a/b-
and IL-12-mediated pathways in promoting
T cell IFN-g responses during viral infection. J. Exp. Med. 189:1315-1327, 1999.
Klimstra, W.B., K.D. Ryman, K.A. Bernard,
K.B. Nguyen, C.A. Biron,
and R.E. Johnston. Infection of neonatal
mice with Sindbis virus results in a systemic
inflammatory response syndrome. J. Virol. 73: 10387-10398, 1999.
Nguyen, K.B., and C.A. Biron.
Synergism for cytokine-mediated disease
during concurrent endotoxin and viral challenges:
roles for natural killer and T cell IFN-g
production. J. Immunol. 162:5238-5246, 1999.
Ruzek, M.C., B.D. Pearce, A.H. Miller, and
C.A. Biron. Endogenous glucocorticoids
protect against cytokine-mediated lethality
during virus infection. J. Immunol. 162:3527-3533, 1999.
She, J., M.C. Ruzek, P. Velupillai, I. de
Aos, B. Wang, D.A. Harn, J. Sancho, C.A.
Biron, and C. Terhorst. Generation
of antigen specific cytotoxic T lymphocytes
and regulation of cytokine production takes
place in the absence of CD3z.
Int. Immunol. 11:845-858, 1999.
Salazar-Mather, T.P., J.S. Orange, and
C.A. Biron. Early murine cytomegalovirus
(MCMV) infection induces liver natural killer
(NK) cell inflammation and protection through
macrophage inflammatory protein 1 a (MIP-1a)-dependent pathways. J. Exp. Med. 187:1-14, 1998.
Su, H.C., L.P. Cousens, L.D. Fast, M.K.
Slifka, R.D. Bungiro, R. Ahmed, and C.A.
Biron. CD4+ and CD8+ T cell interactions
in IFN-g and IL-4 responses to viral infections: requirements for
IL-2. J. Immunol. 160:5007-5017, 1998.
Bonyadi, M., S.A.B. Rusholme, F.M. Cousins,
H.C. Su, C.A. Biron, M.
Farrall, and A.J. Akhurst. Mapping of a
major genetic modifier of embryonic lethality
in TGFb1 knockout
mice. Nature Genetics 15:207-211, 1997.
Cousens, L.P., J.S. Orange, H.C. Su, and
C.A. Biron. Interferon-a/b inhibition of interleukin 12 and interferon-g production in vitro and endogenously during viral infection.
Proc. Natl. Acad. Sci. USA 94:634-639, 1997.
Orange, J.S., T.P. Salazar-Mather, S.M.
Opal, and C.A. Biron. Mechanisms
for virus-induced disease: tumor necrosis
factor-mediated pathology independent of
natural killer and T cells during murine
cytomegalovirus infection. J. Virol. 71:9248-9258, 1997.
Miller, A.H., R.L. Spencer, B.D. Pearce,
T.L. Pisell, P. Tanapat, J.J. Leung, F.S.
Dhabhar, B.S. McEwen, and C.A. Biron.
Effects of viral infection on glucocorticoid
secretion and glucocorticoid receptor binding
in immune tissues. Psychoneuroendocrinology 22:455-474, 1997.
Ruzek, M.C., A.H. Miller, S.M. Opal, B.D.
Pearce, and C.A. Biron.
Characterization of early cytokine responses
and an IL-6-dependent pathway of endogenous
glucocorticoid induction during murine cytomegalovirus
infection. J. Exp. Med. 185:1185-1192, 1997.
Orange, J.S., and C.A. Biron. An
absolute and restricted requirement for
interleukin 12 (IL-12) in natural killer
(NK) cell interferon-g (IFN-g) production and antiviral
defense: studies of NK and T cell responses
in contrasting viral infections.
J. Immunol. 156:1138-1142, 1996.
Salazar-Mather, T.P., R. Ishikawa, and C.A.
Biron. Natural killer (NK) cell
trafficking and cytokine expression in splenic
compartments after IFN induction and viral
infection. J. Immunol. 157:3054-3064, 1996.
Orange, J.S., B. Wang, C. Terhorst, and
C.A. Biron. Requirement
for natural killer (NK) cell-produced interferon
g in defense against murine cytomegalovirus infection and enhancement
of this defense pathway by interleukin 12
administration. J. Exp. Med. 182:1045-1056, 1995.
back to top
LAB
MEMBERS
M. Pilar Gil, Ph.D., Instructor of Medical Science (Research)
Seung-Hwan Lee, Ph.D., Postdoctoral Research Associate
Takuya Miyagi, Ph.D., Postdoctoral Research Associate
Mickael Ploquin, Ph.D. , Postdoctoral Research Associate
Kwangsin (Sinia) Kim, Senior Research Assistant
Erin Rainone, Research Assistant
Katherine Tsubota, Undergraduate Student
|
Research
Summary 