Variation in FCN1 affects biosynthesis of ficolin-1 and is associated with outcome of systemic inflammation
GENES AND IMMUNITY
Authors: Munthe-Fog, L.; Hummelshoj, T.; Honore, C.; Moller, M. E.; Skjoedt, M. O.; Palsgaard, I.; Borregaard, N.; Madsen, H. O.; Garred, P.
Abstract
Ficolin-1 is a recognition molecule of the lectin complement pathway. The ficolin-1 gene FCN1 is polymorphic, but the functional and clinical consequences are unknown. The concentration of ficolin-1 in plasma and FCN1 polymorphisms in positions - 1981 (rs2989727), - 791 (rs28909068), - 542 (rs10120023), - 271 (rs28909976), - 144 (rs10117466) and + 7918 (rs1071583) were determined in 100 healthy individuals. FCN1 expression by isolated monocytes and granulocytes and ficolin-1 levels in monocyte culture supernatants were assessed in 21 FCN1-genotyped individuals. FCN1 polymorphisms were determined in a cohort of 251 patients with systemic inflammation. High ficolin-1 plasma levels were significantly associated with the minor alleles in position - 542 and - 144. These alleles were also significantly associated with high FCN1 mRNA expression. The level of ficolin-1 in culture supernatants was significantly higher in individuals homozygous for the minor alleles at positions - 542 and - 144. Homozygosity for these alleles was significantly associated with fatal outcome in patients with systemic inflammation. None of the other investigated polymorphisms were associated with FCN1 and ficolin-1 expression, concentration or disease outcome. Functional polymorphic sites in the promoter region of FCN1 regulate both the expression and synthesis of ficolin-1 and are associated with outcome in severe inflammation.
Immunosuppression in Cows following Intramammary Infusion of Mycoplasma bovis
INFECTION AND IMMUNITY
Authors: Gondaira, Satoshi; Nishi, Koji; Tanaka, Takahiro; Yamamoto, Takashi; Nebu, Takanori; Watanabe, Reina; Konnai, Satoru; Hayashi, Tomohito; Kiku, Yoshio; Okamoto, Mariko; Matsuda, Kazuya; Koiwa, Masateru; Iwano, Hidetomo; Nagahata, Hajime; Higuchia, Hidetoshi
Abstract
Mycoplasma bovis is a destructive pathogen that causes large economic losses in rearing cattle for beef and dairy worldwide. M. bovis causes suppression of and evades the host immune response; however, the mechanisms of host immune function involved in M. bovis mastitis have not been elucidated. The purpose of this study was to elucidate the characteristics of the bovine immune response to mycoplasmal mastitis. We evaluated the responsiveness of the bovine mammary gland following infusion of M. bovis. Somatic cell counts and bacterial counts in milk from the infected quarter were increased. However, the proliferation of peripheral blood mononuclear cells (blood MNCs) and mononuclear cells isolated from M. bovis-stimulated mammary lymph nodes (lymph node MNCs) did not differ from that in the unstimulated cells. Transcriptome analysis revealed that the mRNA levels of innate immune system-related genes in blood MNCs, complement factor D (CFD), ficolin 1 (FCN1), and tumor necrosis factor superfamily member 13 (TNFSF13) decreased following intramammary infusion of M. bovis. The mRNA levels of immune exhaustion-related genes, programmed cell death 1 (PD-1), programmed cell deathligand 1 (PD-L1), lymphocyte activation gene 3 (LAG3), and cytotoxic T-lymphocyte-associated protein 4 (CTLA4) of milk mononuclear cells (milk MNCs) in the infected quarter were increased compared with those before infusion. Increase in immune exhaustion-related gene expression and decrease in innate immune response-related genes of MNCs in quarters from cows were newly characterized by M. bovis-induced mastitis. These results suggested that M. bovis-induced mastitis affected the immune function of bovine MNCs, which is associated with prolonged duration of infection with M. bovis.