Lipopolysaccharide from Rhodobacter sphaeroides Attenuates Microglia-Mediated Inflammation and Phagocytosis and Directs Regulatory T Cell Response

Sagar Gaikwad, Reena Agrawal-Rajput

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Microglia activation and neuroinflammation are key events during the progression of neurodegenerative disorders. Microglia exhibits toll-like receptors (TLRs), with predominant expression of TLR4, inducing aberrant neuroinflammation and exacerbated neurotoxicity. Studies suggest that microglia initiate infiltration of T cells into the brain that critically influence disease conditions. We report that LPS-Rs, through TLR4 antagonism, significantly inhibit TLR4 mediated inflammatory molecules like IL-1β, IL-6, TNF-α, COX-2, iNOS, and NO. LPS-Rs regulates JNK/p38 MAPKs and p65-NF-κB signaling pathways, which we report as indispensible for LPS induced neuroinflammation. LPS-Rs mitigates microglial phagocytic activity and we are first to report regulatory role of LPS-Rs which blocked microglia mediated inflammation and apoptotic cell death. LPS-Rs significantly inhibits expression of costimulatory molecules CD80, CD86, and CD40. Chemokine receptor, CCR5, and T cell recruitment chemokines, MIP-1α and CCL5, were negatively regulated by LPS-Rs. Furthermore, LPS-Rs significantly inhibited lymphocyte proliferation with skewed regulatory T (Treg) cell response as evidenced by increased FOXP3, IL-10, and TGF-β. Additionally, LPS-Rs serves to induce coordinated immunosuppressive response and confer tolerogenic potential to activated microglia extending neurosupportive microenvironment. TLR4 antagonism can be a strategy providing neuroprotection through regulation of microglia as well as the T cells.

Original languageEnglish (US)
Article number361326
JournalInternational Journal of Inflammation
Volume2015
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

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Rhodobacter sphaeroides
Microglia
Regulatory T-Lymphocytes
Phagocytosis
Lipopolysaccharides
Inflammation
T-Lymphocytes
Chemokine Receptors
Toll-Like Receptors
p38 Mitogen-Activated Protein Kinases
Immunosuppressive Agents
Interleukin-1
Chemokines
Neurodegenerative Diseases
Interleukin-10
Interleukin-6
Cell Death
Lymphocytes
Brain

ASJC Scopus subject areas

  • Immunology and Allergy

Cite this

Lipopolysaccharide from Rhodobacter sphaeroides Attenuates Microglia-Mediated Inflammation and Phagocytosis and Directs Regulatory T Cell Response. / Gaikwad, Sagar; Agrawal-Rajput, Reena.

In: International Journal of Inflammation, Vol. 2015, 361326, 01.01.2015.

Research output: Contribution to journalArticle

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