Chlamydia Research Laboratory

Principal Investigator

Mirja Puolakkainen, MD, PhD
Adjunct Professor of Medical Microbiology
Department of Virology
Room: E457
Tel: +358 2941 26559
Fax: +358 2941 26491
mirja.puolakkainen (at) helsinki.fi

Postdoctoral Fellows

Laura Mannonen, PhD
Juha Korhonen, MD, PhD

Graduate Students

Suvi Niemi, MSc

Main collaborators, Senior Scientists

Jorma Paavonen, professor (Helsinki University Central Hospital, Helsinki, Finland)
Eija Hiltunen-Back, MD, PhD, Specialist (Helsinki University Central Hospital, Helsinki, Finland)
Matthias Mass, Professor (Augsburg, Germany)
Peter Deszo Virok (Szeged, Hungary)
Lee Ann Campbell, Professor (University of Washington, Seattle, USA)

Laboratory: E424
Office: E457

Research interests

The focus of our research is on the pathogenesis of acute and persistent chlamydial infections.

Our group has studied chlamydial infection and the microbe-host cell interaction using diverse models. In vitro, we have shown that C. pneumoniae reprograms the host cells transcriptional machinery: Procoagulant activity and expression of Tissue Factor (Bea et al. 2003) as well as production of 92-kDa gelatinase (Vehmaan-Kreula et al. 2001) are induced in macrophages upon infection. Also, C. pneumoniae can promote inflammation by inducing a pro-inflammatory response in human mast cells and epithelial cells (Oksaharju et al. 2009, Törmäkangas et al. 2010). During persistent C. pneumoniae infection in epithelial cells (Mannonen et al. 2003) transcription of nine host cell genes was consistently altered (Mannonen et al. 2007). We have also studied receptor usage and entry: C. trachomatis can utilize the mannose receptor (Kuo et al. 2002), while C. pneumoniae appears to use other receptors(s), including the mannose 6-P receptor (Puolakkainen et al 2005), and LOX-1, a scavenger receptor on endothelial cells (Campbell et al. 2012). We have recently shown that C. pneumoniae attachment and internalization is dependent on host cell cholesterol but independent of clathrin (Korhonen et al. 2012).

In an experimental murine model of infection, we have shown the essential role of CD8+ T cells and gamma interferon in clearance of infection (Penttilä et al. 1999). Methods for identification of C. pneumoniae derived CD8-epitopes (Sarén et al. 2002) and for characterization of the HLA-A2.1-restricted CD8 T-cell responses during infection were developed (Tammiruusu et al. 2005). Partial protective immunity was induced by DNA or viral vector vaccines expressing C. pneumoniae proteins (Penttilä et al. 2000, 2004) or by administration of CopN protein (Tammiruusu et al. 2007). Local IgA antibodies correlated with the protection (Penttilä et al. 2006). While IL-10 suppressed inflammation during experimental infection, it also increased bacterial burden (Penttilä et al. 2008). The immune response developing during infection was characterized by profiling gene expression in lymphocytes (Kyläniemi et al. 2009).

Research methods, including experimental infection model in vitro and its characterization, gene expression analysis by microarray and real time RT-PCR, transfection, RNAi, fluorescence microscopy, and quantitative methods for detection of Chlamydiae are already well established. Our studies will contribute to the understanding of the unique relationship between Chlamydiae and the host cell, and of the disease process of Chlamydial infection and its clinical outcomes. Furthermore, the knowledge obtained in these studies will have a potential use in two clearly defined areas: development of a diagnostic tool for the detection of persistent infection, and identification of novel target molecules for therapy of chlamydial infections.

Selected Publications

• Bea F*, Puolakkainen MH*, McMillen T, Hudson FN, Mackman N, Kuo CC, Campbell LA, Rosenfeld ME. Chlamydia pneumoniae Activates Tissue Factor Expression in Mouse Macrophages via Egr-1. Circ Research, 92:394-401;2003. * equal contribution

• Mannonen L, Kamping E, Penttila T, Puolakkainen M. IFN-I induced persistent Chlamydia pneumoniae infection in HL and Mono Mac 6 cells: Characterization by real-time quantitative PCR and culture. Microb Pathog, 36:41-50;2004

• Puolakkainen M, Kuo C-C, and Campbell LA. Chlamydia pneumoniae uses the mannose 6-phosphate/insulin-like growth factor 2 receptor for infection of endothelial cells. Infect Immun, 73:4620-4625;2005.

• Mannonen L, Nikula T, Haveri A, Reinikainen A, Vuola JM, Lahesmaa R, Puolakkainen M. Upregulation of host cell genes during interferon-gamma induced persistent Chlamydia pneumoniae infection in HL cells. J Infect Dis, 195:212-219;2007.

• Törmäkangas L, Markkula E, Lounatmaa K, Puolakkainen M. Chlamydia pneumoniae infection in polarized epithelial cell lines. Infect Immun 78:2714-22;2010.

• Korhonen JT, Puolakkainen M, Haveri A, Tammiruusu A, Sarvas M, Lahesmaa R. Chlamydia pneumoniae entry into epithelial cells by clathrin-independent endocytosis. Microbial Pathogenesis, 52:157-64;2012.

• Korhonen JT, Puolakkainen M, Häivälä R, Penttilä T, Haveri A, Markkula E, and Lahesmaa R. Flotillin-1/reggie-2 contributes to Chlamydia pneumoniae growth and associates with bacterial inclusion. Infect Immun 80:1072-8;2012.

• Korhonen S, Hiltunen-Back E, Puolakkainen M. Genotyping of Chlamydia trachomatis in rectal and pharyngeal specimens: Identification of LGV genotypes in Finland. Sex Trans Inf, Apr 19, 2012. [Epub ahead of print].