Anu Haveri

Chlamydia pneumoniae infection in IL-10 knock out mice: Accelerated clearance but severe pulmonary inflammatory response☆

In interleukin-10 knock out (IL-10 KO) mice, accelerated clearance of pulmonary Chlamydia pneumoniae infection was observed. On the other hand, the histopathological changes in lung tissue were more pronounced in IL-10 KO mice at all time points after infection and repeated infection than in the wild type mice. Both ex vivo induced antigen-specific proliferation as well as production of proinflammatory cytokines by splenocytes were higher in IL-10 KO mice than in WT mice. Also, intrapulmonary proinflammatory cytokine levels were higher in IL-10 KO mice than in the WT mice. The lack of anti-inflammatory action of IL-10 is likely to contribute to the enhanced clearance but severe inflammation in this experimental model.

Reduced cross-protection against influenza A(H3N2) subgroup 3C.2a and 3C.3a viruses among Finnish healthcare workers vaccinated with 2013/14 seasonal influenza vaccine

Virus strains in the seasonal influenza vaccine for the 2014/15 northern hemisphere season remained unchanged from those in 2013/14. During spring 2014, drifted influenza A(H3N2) viruses, subgroup 3C.3a, were detected in Finland; another subgroup, 3C.2a, emerged in the 2014/15 season and has predominated. We monitored antibody responses against vaccine and epidemic strains (2013/14 and 2014/15) among Finnish healthcare workers after influenza vaccination with the 2013/14 vaccine. The data suggest reduced cross-protection towards both subgroups of drifted A(H3N2) viruses.

Up‐Regulation of Host Cell Genes during Interferon‐γ-Induced Persistent Chlamydia pneumoniae Infection in HL Cells

As a step toward understanding the role played by host gene expression in the development and pathogenesis of persistent Chlamydia pneumoniae infection, modulation of the host-cell transcriptional response during interferon (IFN)- gamma -induced persistent C. pneumoniae infection of HL cells was examined by a cDNA array and then selectively by a real-time quantitative reverse transcription-polymerase chain reaction. We identified 9 host cell genes whose transcription was consistently altered during IFN- gamma -induced persistent C. pneumoniae infection. The strongest up-regulation of persistent infection, compared with controls (active infection and IFN- gamma ) was identified for insulin-like growth factor-binding protein 6, IFN-stimulated protein 15 kDa, cyclin D1, and interleukin-7 receptor genes. These results suggest that, during persistent infection, C. pneumoniae reprograms the host transcriptional machinery that regulates a variety of cellular processes, including adhesion, regulation of the cell cycle, growth, and inflammatory response, all of which might play important roles in the pathogenesis of persistent C. pneumoniae infection.

Flotillin-1 (Reggie-2) Contributes to Chlamydia pneumoniae Growth and Is Associated with Bacterial Inclusion

ABSTRACT Chlamydiae are obligate intracellular pathogens replicating only inside the eukaryotic host. Here, we studied the effect of human flotillin-1 protein on Chlamydia pneumoniae growth in human line (HL) and A549 epithelial cell lines. RNA interference was applied to disrupt flotillin-1-mediated endocytosis. Host-associated bacteria were detected by quantitative PCR, and C. pneumoniae growth was evaluated by inclusion counts. C. pneumoniae attachment to host cells was unaffected, but bacterial intracellular growth was attenuated in the flotillin-1-silenced cells. By using confocal microscopy, we detected flotillin-1 colocalized with the inclusion membrane protein A (IncA) in the C. pneumoniae inclusion membranes. In addition, flotillin-1 was associated with IncA in detergent-resistant membrane microdomains (DRMs) in biochemical fractioning. These results suggest that flotillin-1 localizes to the C. pneumoniae inclusion membrane and plays an important role for intracellular growth of C. pneumoniae.

Mid-season real-time estimates of seasonal influenza vaccine effectiveness in persons 65 years and older in register-based surveillance, Stockholm County, Sweden, and Finland, January 2017

Systems for register-based monitoring of vaccine effectiveness (VE) against laboratory-confirmed influenza (LCI) in real time were set up in Stockholm County, Sweden, and Finland, before start of the 2016/17 influenza season, using population-based cohort studies. Both in Stockholm and Finland, an early epidemic of influenza A(H3N2) peaked in week 52, 2016. Already during weeks 48 to 50, analyses of influenza VE in persons 65 years and above showed moderately good estimates of around 50%, then rapidly declined by week 2, 2017 to 28% and 32% in Stockholm and Finland, respectively. The sensitivity analyses, where time since vaccination was taken into account, could not demonstrate a clear decline, neither by calendar week nor by time since vaccination. Most (68%) of the samples collected from vaccinated patients belonged to the 3C.2a1 subclade with the additional amino acid substitution T135K in haemagglutinin (64%) or to subclade 3C.2a with the additional haemagglutinin substitutions T131K and R142K (36%). The proportion of samples containing these alterations increased during the studied period. These substitutions may be responsible for viral antigenic change and part of the observed VE drop. Another possible cause is poor vaccine immunogenicity in older persons. Improved influenza vaccines are needed, especially for the elderly.

Gene expression signatures characterizing the development of lymphocyte response during experimental Chlamydia pneumoniae infection.

In this study experimental mouse model for Chlamydia pneumoniae infection was used to elucidate the nature of immune response developing during primary and secondary infection. First we examined the mononuclear cells from different lymphoid organs in BALB/c mice during C. pneumoniae infection and detected a strong lymphocyte influx into mediastinal lymph nodes (MLN). To further characterize the C. pneumoniae induced immune response the gene expression profiles of MLN derived lymphocytes was studied. To identify genes characteristic for reinfection we compared gene expression profiles during reinfection and primary infection and found 148 genes to be differentially regulated in CD19+ cells, 7 in CD4+ cells and 12 in CD8+ cells. A panel of these genes was selected to be confirmed by real-time RT-PCR. Genes related to interferon signaling like Ifit1, Ifit3, Gbp2, Irf7 and Usp18 were found to be upregulated when reinfection was compared to primary infection. In our study we were able to identify 8 genes that were differentially expressed between reinfection and primary infection in lymphocytes. These novel gene expression signatures provide new insights and clues to the nature of protective immunity established during experimental C. pneumoniae immunity.

A cluster of measles linked to an imported case, Finland, 2017

One imported and five secondary cases of measles were detected in Finland between June and August 2017. The measles sequences available for five laboratory-confirmed cases were identical and belonged to serotype D8. The large number of potentially exposed Finnish and foreign individuals called for close cooperation of national and international public health authorities and other stakeholders. Raising awareness among healthcare providers and ensuring universally high vaccination coverage is crucial to prevent future clusters and outbreaks.