Abstract / Journal of Reproductive Immunology 101–102 (2014) 18–39 19

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Influenza A virus infection and pregnancy in mice:reduced ability of leukocyte homing to the lung and highvirus mutation rate account for enhanced gestationalmorbidity and mortality

Géraldine L. Engels 1,2,∗,5, René Thieme 2,5, JuliaHoffmann 1,5, Hans-Willi Mittrücker 3, Khalil Karimi 4,Gülsah Gabriel 1,6, Petra C. Arck 2,6

1 Heinrich Pette Institute, Leibniz Institute for ExperimentalVirology, Hamburg, Germany2 Department of Obstetrics and Fetal Medicine, Laboratoryfor Experimental Feto-Maternal Medicine, University MedicalCenter Hamburg-Eppendorf, Hamburg, Germany3 Institute for Immunology, University Medical CenterHamburg-Eppendorf, Hamburg, Germany4 Institute for Experimental Immunology and Hepatology,University Medical Center Hamburg-Eppendorf, Hamburg,Germany

Infectious diseases pose a severe threat to women dur-ing pregnancy, as unveiled by the enhanced disease riskfor pregnant women during the 2009 H1N1 influenza pan-demic. Here, mortality and morbidity rates were higheramong infected pregnant women, which was unprece-dented, compared with previous, seasonal H1N1 influenzainfections. In consequence, the World Health Organisa-tion revised its vaccine recommendations, now advisingprioritized vaccination for pregnant women. Nonetheless,insights into viral or immunological determinants that ren-der pregnant women highly susceptible to influenza aresparse. Published evidence suggests that during murinepregnancy, decidual stromal cells might be unable torecruit effector T cells to the uterus owing to epigeneticsilencing of CXCR3 chemokine receptor ligands. Recruit-ment of effector T cells to the lung is a key response elementto clear influenza virus infection. We here aimed to identifywhether altered chemokine expression in the lung mightaccount for an increased influenza risk during pregnancy.

We established a mouse model in which BALB/c-matedpregnant C57Bl/6 females were infected with 103 plug-forming units of a H1N1 virus strain. The females mirrorepidemiological findings seen in humans, i.e. increasedinfluenza morbidity and mortality. We identified thatmRNA expression of the C-X-C motif chemokine 10(CXCL10), a CXCR3 ligand, is significantly lower in lungsof infected pregnant mice compared with non-pregnantmice. The reduced CXCL10 expression was associated witha reduced frequency of leukocytes in the lung. Using trans-criptome analyses, we found that the viral genome rapidlyaccumulates numerous mutations during the course ofinfection in the lungs of infected dams compared withnon-pregnant infected mice. Our data suggest that theco-incidence of an influenza infection during pregnancycreates a contradictory demand for the maternal immunesystem, rendering the dams unable to mount the required

5 Authors contributed equally.6 Joint supervision.

immune response to combat influenza virus infection, suchas recruitment of virus-specific effector T cells. This insuffi-cient immune response likely results in viral escape by therapid emergence of viral genotype variants in the pregnanthost. This perpetuates the inability to mount a tailoredimmune response to the influenza virus strains. This viciouscycle may account for the high influenza-related morbidityand mortality during pregnancy.

http://dx.doi.org/10.1016/j.jri.2013.12.077

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Influence of glucose on cytokine production in patientswith gestational diabetes

Silvia Daher ∗, Karen Pendeloski K.P.T., Thalita. F. Lobo,Thais W. Siqueira, Rosiane Mattar, M.R. Torloni

Department of Obstetrics, Universidade Federal de Sao Paulo,Sao Paulo, Brazil

Background: Gestational diabetes (GD) is the most fre-quent metabolic disorder of pregnancy. GD is associatedwith increased risks of maternal and perinatal compli-cations and also long-term consequences such as type 2diabetes mellitus (T2DM) in the mother and early onsetof metabolic syndrome, obesity and T2DM in childrenexposed to GD during fetal life. High levels of glucose foundin women with GD may be related to the typical abnormalinflammatory response of this disease. We aimed to ana-lyze the influence of glucose on the in vitro production ofinflammatory mediators in pregnant women with GD.

Methods: This cross-sectional study collected bloodfrom women with GD at 28–36 weeks’ gestation, whenthey were performing a routine 75 g oral glucose toler-ance test (OGTT) to detect GD as part of their standardantenatal care. PBMC was cultured in RPMI medium, withand without glucose (25 mM). All cultures were stimulatedwith LPS for 48 h. Culture supernatant TNFA and IL-6 con-centrations were determined by ELISA. Data were analyzedusing Student’s t test. This study was approved by the EthicsCommittee.

Results: There were no differences in TNFA (p = 0.11)and IL-6 (p = 0.72) levels in supernatant culture with andwithout glucose 25 mM stimulated with LPS for 48 h.

Conclusions: Glucose does not seem to stimulate the invitro production of inflammatory cytokines in women withGD.

Financial support: FAPESP (11/14554-2 and 10/52547-5) and CAPES.

http://dx.doi.org/10.1016/j.jri.2013.12.078