Viral and bacterial co-infection in severe pneumonia triggers innate immune responses and specifically enhances IP-10: a translational study.
Viral and bacterial co-infection in severe pneumonia triggers innate immune responses and specifically enhances IP-10: a translational study.
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DOI：
10.1038/srep38532
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发表时间：
2016-12-06
影响因子：
4.6
通讯作者：
Paranhos-Baccalà G
中科院分区：
文献类型：
--
作者：
Hoffmann J;Machado D;Terrier O;Pouzol S;Messaoudi M;Basualdo W;Espínola EE;Guillen RM;Rosa-Calatrava M;Picot V;Bénet T;Endtz H;Russomando G;Paranhos-Baccalà G
病毒和细菌混合感染在社区获得性肺炎中被广泛描述;然而，联合感染对相关免疫病理学的临床意义仍然研究不足。在这项研究中，microRNA，mRNA和细胞因子/趋化因子的分泌谱进行了研究的人单核细胞来源的巨噬细胞感染流感病毒A/H1N1和/或肺炎链球菌在体外。我们观察到，与单一感染细胞条件相比，体外共感染协同增加干扰素-γ诱导蛋白-10（CXCL 10，IP-10）表达。我们证明了内源性miRNA-200 a-3 p，其表达在共感染后协同诱导，通过靶向细胞因子信号传导抑制因子-6（SOCS-6）（JAK-STAT信号传导途径的一种众所周知的调节因子）间接调节CXCL 10表达。此外，在随后的临床初步研究中，在74名因病毒性和/或细菌性社区获得性肺炎住院的儿童（≤5岁）的样本中评价了免疫调节剂水平。临床上，在74例肺炎患者中，混合检测者血清IP-10水平明显高于单一检测者（3.6倍）（P = 0.03），且与重症肺炎显著相关（P < 0.01）。这项研究表明，病毒和细菌共感染调节JAK-STAT信号通路，并导致IP-10表达加剧，这可能在肺炎的发病机制中发挥重要作用。
Mixed viral and bacterial infections are widely described in community-acquired pneumonia; however, the clinical implications of co-infection on the associated immunopathology remain poorly studied. In this study, microRNA, mRNA and cytokine/chemokine secretion profiling were investigated for human monocyte-derived macrophages infected in-vitro with Influenza virus A/H1N1 and/or Streptococcus pneumoniae. We observed that the in-vitro co-infection synergistically increased interferon-γ-induced protein-10 (CXCL10, IP-10) expression compared to the singly-infected cells conditions. We demonstrated that endogenous miRNA-200a-3p, whose expression was synergistically induced following co-infection, indirectly regulates CXCL10 expression by targeting suppressor of cytokine signaling-6 (SOCS-6), a well-known regulator of the JAK-STAT signaling pathway. Additionally, in a subsequent clinical pilot study, immunomodulators levels were evaluated in samples from 74 children (≤5 years-old) hospitalized with viral and/or bacterial community-acquired pneumonia. Clinically, among the 74 cases of pneumonia, patients with identified mixed-detection had significantly higher (3.6-fold) serum IP-10 levels than those with a single detection (P = 0.03), and were significantly associated with severe pneumonia (P < 0.01). This study demonstrates that viral and bacterial co-infection modulates the JAK-STAT signaling pathway and leads to exacerbated IP-10 expression, which could play a major role in the pathogenesis of pneumonia.
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DOI：
10.1086/591708
发表时间：
2008-10-01
期刊：
The Journal of infectious diseases
影响因子：
--
作者：
Morens DM;Taubenberger JK;Fauci AS
通讯作者：
Fauci AS
影响因子：
3.7
作者：
Messaoudi M;Milenkov M;Albrich WC;van der Linden MP;Bénet T;Chou M;Sylla M;Barreto Costa P;Richard N;Klugman KP;Endtz HP;Paranhos-Baccalà G;Telles JN
通讯作者：
Telles JN
影响因子：
3.6
作者：
Nascimento-Carvalho, Cristiana M.;Ribeiro, Catarina T.;Ruuskanen, Olli
通讯作者：
Ruuskanen, Olli
影响因子：
10
作者：
Lahti, E.;Peltola, V.;Ruuskanen, O.
通讯作者：
Ruuskanen, O.
影响因子：
1.7
作者：
Marriott, Helen M.;Dockrell, David H.
通讯作者：
Dockrell, David H.