High expression levels of macrophage migration inhibitory factor sustain the innate immune responses of neonates

Thierry Roger, Anina Schneider, Manuela Weier, Fred C. G. J. Sweep, Didier Le Roy, Jürgen Bernhagen, Thierry Calandra, and Eric Giannoni.

PNAS. (2016) E997–E1005

Speaker: Yi Tien (田 依)                                              Time: 13:00~14:00, Oct. 05, 2016

Commentator: Dr. Chi-Chang Shieh (謝奇璋教授)     Place: Room 601

Abstract

Human newborns suffer a high frequency and severity of invasive microbial infections compared with healthy adults. [1] Previous studies have investigated that high expression levels of adenosine and prostaglandins reduce the antimicrobial responses of neonatal immune cells. [2] Notably, newborns express 10-fold higher levels of pro-inflammatory immune regulator migration inhibitory factor (MIF) compared with adults. MIF is capable of modulating both innate and adaptive immune responses in several disease including viral and bacterial infection. [3] The authors hypothesized that newborns have counterregulatory mechanisms to balance neonatal immunosuppression and explored whether MIF could be involved in. In this study, the authors used three strategies to investigate the impact of MIF on the innate immune response. First, inhibition of MIF activity by ISO-1 and reduction of MIF expression by siRNA decreased cytokine production in newborn monocytes which were exposed to microbial. Importantly, recombinant human MIF treatment restored E.coli-induced cytokine production in MIF-silenced monocytes. In addition, the authors further investigated whether MIF could counterregulate immunosuppression by high circulating levels of hormones. They found that adenosine and prostaglandins-mediated inhibition of ERK1/2 MAPK signaling through MIF to counterbalance. Altogether, these results revealed that newborns have developed mechanisms to maintain the innate immune system balance during neonatal period. This study provided a potential attractive target for immune-modulating adjunctive therapies for neonatal severe microbial infections.

References:

1.         Kollmann TR, et al. J Immunol 183(11):7150–7160. (2009) Neonatal innate TLR -mediated responses are distinct from those of adults.

2.         Giannoni E, et al. Infect Immun 79(7):2690–2698. (2011) Estradiol and progesterone strongly inhibit the innate immune response of mononuclear cells in newborns. 

3.         Calandra, T. and T. Roger, et al. Nat Rev Immunol, 3(10):p.791-800. (2003) Macrophage migration inhibitory factor: a regulator of innate immunity.