MyD88-dependent expansion of an immature GR-1+CD11b+ population induces T cell suppression and Th2 polarization in sepsis

By M. Delano, P. Scumpia, J. Weinstein, Dominique P. Coco, S. Nagaraj, K. Kelly-Scumpia, Kerri A. O’Malley, J. Wynn, S. Antonenko, S. Al-Quran and 12 more. Journal of Experimental Medicine, 2007

700 citations recorded by the source corpus.

Polymicrobial sepsis alters the adaptive immune response and induces T cell suppression and Th2 immune polarization. We identify a GR-1+CD11b+ population whose numbers dramatically increase and remain elevated in the spleen, lymph nodes, and bone marrow during polymicrobial sepsis. Phenotypically, these cells are heterogeneous, immature, predominantly myeloid progenitors that express interleukin 10 and several other cytokines and chemokines. Splenic GR-1+ cells effectively suppress antigen-specific CD8+ T cell interferon (IFN) γ production but only modestly suppress antigen-specific and nonspecific CD4+ T cell proliferation. GR-1+ cell depletion in vivo prevents both the sepsis-induced augmentation of Th2 cell–dependent and depression of Th1 cell–dependent antibody production. Signaling through MyD88, but not Toll-like receptor 4, TIR domain–containing adaptor-inducing IFN-β, or the IFN-α/β receptor, is required for complete GR-1+CD11b+ expansion. GR-1+CD11b+ cells contribute to sepsis-induced T cell suppression and preferential Th2 polarization.

Subfields: Epidemiology, Immunology

View Paper: https://www.semanticscholar.org/paper/d657c2159a65030740b5c636404c6d330395ae4e

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Epidemiology

1. TA Wynn
2. P. Murray
3. S. V. Van Dyken
4. R. Locksley
5. R. Medzhitov
6. Y. Okabe

In Immunology

1. D. Gabrilovich
2. S. Ostrand-Rosenberg
3. TA Wynn
4. T. Condamine
5. P. Sinha
6. S. Galli
7. P. Murray
8. Xiangming Zou

Citations in the corpus

• Protective and pathogenic functions of macrophage subsets (2011, background): “and smouldering sepsis induced by caecal ligation and puncture (CLP”
• Molecular mechanisms regulating myeloid-derived suppressor cell differentiation and function (2010, background): “NF-κB, acting downstream of MyD88, is required for accumulation of MDSCs in a model of polymicrobial sepsis[54].”
• Immunosuppression in Patients Who Die of Sepsis and Multiple Organ Failure (2011, unknown): “0) [24-84] Sex Male 17 Female 12 Admission diagnosis Motor vehicle collision, head trauma 1”
• Resolution of inflammation: an integrated view (2013, unknown): “MDSCs exert beneficial activities in inflammatory conditions such as sepsis, inflammatory bowel disease, autoimmune encephalomyelitis and multiple sclerosis (Delano et al, 2007; Haile et al, 2008; Zhu et al, 2007).”
• Macrophage Polarization in Inflammatory Diseases (2014, background): “Clinical or laboratory evidence for sepsis being an immunosuppressive disorder has been proposed by Hotchkiss [87]: apoptosis of the immune cells, relative increase in regulatory T cells [88] as well as myeloid derived suppressor cells [89], thereby weakening the defense to pathogens.”
• Myeloid-Derived Suppressor Cells: Linking Inflammation and Cancer (2009, background): “This alternative pathway is likely to be mediated by other TLR ligands, because mice deleted for MyD88, an adaptor protein in the signaling pathway of most TLRs, do not accumulate high levels of MDSC in response to sepsis (20).”