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Review
. 2022 Dec 1:9:995044.
doi: 10.3389/fmed.2022.995044. eCollection 2022.

Immune modulation after traumatic brain injury

Marwan Bouras  1   2 , Karim Asehnoune  1   2 , Antoine Roquilly  1   2
Affiliations
Review

Immune modulation after traumatic brain injury

Marwan Bouras et al. Front Med (Lausanne). .

Abstract

Traumatic brain injury (TBI) induces instant activation of innate immunity in brain tissue, followed by a systematization of the inflammatory response. The subsequent response, evolved to limit an overwhelming systemic inflammatory response and to induce healing, involves the autonomic nervous system, hormonal systems, and the regulation of immune cells. This physiological response induces an immunosuppression and tolerance state that promotes to the occurrence of secondary infections. This review describes the immunological consequences of TBI and highlights potential novel therapeutic approaches using immune modulation to restore homeostasis between the nervous system and innate immunity.

Keywords: immunomodulatory therapy; immunosuppression; inflammation; innate immunity; traumatic brain injury.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Innate immune response in brain: After TBI, parenchymal, vascular, and blood-brain barrier damage results in the production of DAMPs. These DAMPs activate resident brain cells (microglia, astrocytes) that initiate the intracerebral inflammatory response. The production of cytokines and chemokines leads to the recruitment of blood leukocytes and the activation of complement and coagulation pathways. All these phenomena maintain the state of intracerebral inflammation which causes edema and induces a systematization of the immune response.
FIGURE 2
FIGURE 2
HPA axis and autonomic nervous system (i.e., sympathetic nervous system and parasympathetic nervous system) plays central role in regulating peripheral immune cells after TBI. After a TBI, the sympathetic and parasympathetic nervous systems stimulate the secondary lymphoid organs via their neurotransmitters (norepinephrine and acetycholine respectively) leading to a state of immunodepression due to the loss of inflammatory functions of the leukocytes. Post-traumatic activation of HPA axis leads to CIRCI and deepens the immunosuppressive state. α/β AR, α/β adrenergic receptor; α7nAchR, α7 subunit of the acetyl choline receptor.
FIGURE 3
FIGURE 3
TBI induces alterations in immune cells: These immune alterations concern myeloid and lymphoid cells, starting in the bone marrow and lymphoid organs and then in the circulating cells. It is an alteration of the first line of defense (neutrophils) and an inability of the monocyte & macrophages to maintain the inflammatory response. Dendritic cells lose their ability to present antigen and secrete pro-inflammatory cytokines. All these cells develop a tolerogenic phenotype unable to initiate the lymphocyte response, which leads to an expansion of regulatory T cells. All these mechanisms induce a phenomenon called post-traumatic immunodepression and favors the occurrence of nosocomial infections.
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