Activation of myeloid TLR4 Mediates T lymphocyte polarization after traumatic brain injury

Molly Braun, Kumar Vaibhav, Nancy Saad, Sumbul Fatima, Darrell W. Brann, John R. Vender, Lei P. Wang, Md Nasrul Hoda, Babak Baban, Krishnan M. Dhandapani

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Traumatic brain injury (TBI) is a major public health issue, producing significant patient mortality and poor long-Term outcomes. Increasing evidence suggests an important, yet poorly defined, role for the immune system in the development of secondary neurologic injury over the days and weeks following a TBI. In this study, we tested the hypothesis that peripheral macrophage infiltration initiates long-lasting adaptive immune responses after TBI. Using a murine controlled cortical impact model, we used adoptive transfer, transgenic, and bone marrow chimera approaches to show increased infiltration and proinflammatory (classically activated [M1]) polarization of macrophages for up to 3 wk post-TBI. Monocytes purified from the injured brain stimulated the proliferation of naive T lymphocytes, enhanced the polarization of T effector cells (TH1/TH17), and decreased the production of regulatory T cells in an MLR. Similarly, elevated T effector cell polarization within blood and brain tissue was attenuated by myeloid cell depletion after TBI. Functionally, C3H/HeJ (TLR4 mutant) mice reversed M1 macrophage and TH1/TH17 polarization after TBI compared with C3H/OuJ (wild-Type) mice. Moreover, brain monocytes isolated from C3H/HeJ mice were less potent stimulators of T lymphocyte proliferation and TH1/TH17 polarization compared with C3H/OuJ monocytes. Taken together, our data implicate TLR4-dependent, M1 macrophage trafficking/polarization into the CNS as a key mechanistic link between acute TBI and long-Term, adaptive immune responses.

Original languageEnglish (US)
Pages (from-to)3615-3626
Number of pages12
JournalJournal of Immunology
Volume198
Issue number9
DOIs
StatePublished - May 1 2017

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T-Lymphocytes
Macrophages
Monocytes
Adaptive Immunity
Brain
Nervous System Trauma
Th17 Cells
Adoptive Transfer
Inbred C3H Mouse
Regulatory T-Lymphocytes
Myeloid Cells
Traumatic Brain Injury
Brain Injuries
Immune System
Public Health
Bone Marrow
Mortality

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Activation of myeloid TLR4 Mediates T lymphocyte polarization after traumatic brain injury. / Braun, Molly; Vaibhav, Kumar; Saad, Nancy; Fatima, Sumbul; Brann, Darrell W.; Vender, John R.; Wang, Lei P.; Hoda, Md Nasrul; Baban, Babak; Dhandapani, Krishnan M.

In: Journal of Immunology, Vol. 198, No. 9, 01.05.2017, p. 3615-3626.

Research output: Contribution to journalArticle

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