Interferon-γ-producing immature myeloid cells confer protection against severe invasive group A Streptococcus infections

Matsumura T., Ato M., Ikebe T., Ohnishi M., Watanabe H. & Kobayashi K.

Nat. Commun. 2012, 3: 678. doi: 10.1038/ncomms1677

Speaker: Chi-Hua Lee (李季樺)                    )                                 Time:14:00~15:00, Dec. 19, 2012

Commentator: Dr. Yee-Shin Lin (林以行 老師)       )  Location: Room 601

Abstract:     

Streptococcus pyogenes (group A Streptococcus; GAS) is one of the most common human pathogens, which causes skin infection, streptococcal toxic shock syndrome (STSS) and necrotizing fasciitis¹. Myeloid cells, one of the white blood cell types including polymorphonuclear leukocytes (PMNs), can be fully activated by interferon-γ(IFN-γ) to protect cells against GAS infection. IFN-γ known as type Ⅱ interferon, which is a cytokine produced by T-lymphocytes and NK cells, is critical for innate and adaptive immunity against viral and intracellular bacterial infections¹. In this study, the authors demonstrated that immature myeloid cells with ring-shaped nuclei in the peritoneal cavity, skin, spleen, kidney, peripheral blood and bone marrow can produce IFN-γin vivo during early stage of severe invasive GAS infection. The authors showed that IFN-γadministration treatmentreduced the numbers of bacteria in the blood, and. Furthermore, the authors showed that IFN-γ-producing immature myeloid cells (γIMCs) can survive in under the treatment of the granulocyte-macrophage-colony-stimulating factor (GM-CSF), which functions as a white blood cell growth factor. These γIMCs express phenotypic the markers of monocyte and granulocyte and also produce nitric oxide. It is reported that Myeloid-derived suppressor cells (MDSCs) with a the ring-shaped nucleiei are usually referreddefined as PMNs and present in the peripheral blood of the myeloproliferativedisease patients² with myeloproliferative disease². MDSCs show a suppressive effect on T-cell immunity in chronic infections of intracellular pathogens. Further, theyThe authors further revealed that MDSCs are similar to γIMCs in terms of surface markers, dependency on a the growth factor (GM-CSF) and cytokine production profile (IFN-γ), but they these cells did not produce IFN-γin response to in vitro GAS infection. Finally, by using wild type and IFN-γknockout mice (Ifng^-/-) mice together with severe invasive GAS infection, they the authors verified that IFN-γcan improve the bacterial clearance but are detrimental to mice survive after systemic IFN-γtreatment. In conclusion, the authors proved that GM-CSF-dependent γIMCs, a novel class of differentiated granulocytic ring cells, is the major source of IFN-γproduction during early phase of severe invasive GAS infection and have a protective role against infections.

References:

1.      Counningham, M. W. 2002. Pathogenesis of group A streptococcal infections. Clin. Microbiol. Rev. 13, 470-511.

2.      Langenhuijsen, M. M. 1984. Neutrophils with ring-shaped nuclei in myeloproliferative disease. Br. J. Haematol. 58, 227–230.