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Chlamydia pneumoniae induces interleukin-12 responses in peripheral blood mononuclear cells in asthma and the role of toll like receptor 2 versus 4: a pilot study

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Abstract

Background

Chlamydia pneumoniae causes respiratory infection in adults and children, and has been associated with asthma exacerbations and induction of Immunoglobulin (Ig) E responses. We previously reported that C. pneumoniae enhances T helper (Th) 2 responses of peripheral blood mononuclear cells (PBMC) from asthmatic patients. It is likely that toll like receptor (TLR)-2 and TLR-4 mediate cytokine responses and host defense against C. pneumoniae. Thus, we sought to determine whether engagement of TLR-2 or TLR-4 may induce IL-12 production in our C. pneumoniae model.

Methods

PBMC (1.5 × 106) from asthmatic patients (N = 10) and non-asthmatic controls (N = 5) were infected or mock-infected for 1 h ± C. pneumoniae TW183 at a multiplicity of infection (MOI) = 1 and MOI = 0.1, and cultured for 48 h ± anti- TLR-2 and TLR-4 antibodies (Abs) (1 mg/mL). Interleukin (IL)-12 (48 h p.i.) and total IgE levels (day 10) were measured in supernatants (ELISA).

Results

High IgE levels were detected in supernatants of C. pneumoniae- infected PBMC from asthmatics on day 10, compared with mock-infected PBMC (p < 0.03). In contrast, IgE was not detected (<0.3 ng/mL) in either C. pneumoniae infected or mock-infected PBMC from non-asthmatics. IL-12 production by C. pneumoniae-infected asthmatic and non-asthmatic PBMC were similar. When anti-TLR4, but not anti-TLR2, was included in culture, IL-12 production by C. pneumoniae- infected asthmatic PBMC decreased.

Conclusions

C. pneumoniae infection induces IgE production and modulates IL-12 responses in patients with asthma, which may be caused, in part, by differences in TLR-2 and TLR-4 stimulation.

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Abbreviations

C. pneumoniae :

Chlamydia pneumoniae

Ab:

Antibodies

IFN-γ:

Interferon γ

IL:

Interleukin

Ig:

Immunoglobulin

MIF:

Microimmunofluorescence

PBMC:

Peripheral blood mononuclear cells

Th:

T helper

TLR:

Toll like receptor

TNF-α:

Tumor necrosis factor alpha

ELISA:

Enzyme-linked immunosorbent assay

PAMPs:

Pathogen-associated molecular patterns

References

  1. Emre U, Roblin PM, Gelling M et al (1994) The association of Chlamydia pneumoniae infection and reactive airway disease in children. Arch Pediatr Adolesc Med 148:727–731

    Article  CAS  PubMed  Google Scholar 

  2. Biscione GL, Corner J, Chauhan AJ et al (2004) Increased frequency of detection of Chlamydophila pneumoniae in asthma. Eur Resp J 24:745–749

    Article  CAS  Google Scholar 

  3. Airenne S, Surcel HM, Alakarppa H et al (1999) Chlamydia pneumoniae infection in human monocytes. Infect Immun 67:1445–1449

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Halme S, Latvala J, Karttunen R et al (2000) Cell-mediated immune response during primary Chlamydia pneumoniae infection. Infect Immun 68:7156–7158

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Redecke V, Dalhoff K, Bohnet S, Braun J, Maass M (1998) Interaction of Chlamydia pneumoniae and human alveolar macrophages: infection and inflammatory response. Am J Respir Cell Mol Biol 19:721–727

    Article  CAS  PubMed  Google Scholar 

  6. Stahl PD, Ezekowitz RA (1998) The mannose receptor is a pattern recognition receptor involved in host defense. Curr Opin Immunol 10:50–55 (review)

  7. Takeuchi O, Hoshino K, Kawai T et al (1999) Differential roles of TLR2 and TLR4 in recognition of gram-negative and gram-positive bacterial cell wall components. Immunity 11:443–451

    Article  CAS  PubMed  Google Scholar 

  8. Akira S, Takeda K, Kaisho T (2001) Toll-like receptors: critical proteins linking innate and acquired immunity. Nat Immunol 2:675–680

    Article  CAS  PubMed  Google Scholar 

  9. Halme S, Latvala J, Karttunen R et al (2000) Cell-mediated immune response during primary Chlamydia pneumoniae infection. Infect Immun 68:7156–7158

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Trinchieri G (1995) Interleukin-12: a proinflammatory cytokine with immunoregulatory functions that bridge innate resistance and antigen-specific adaptive immunity. Annu Rev Immunol 13:251–276

    Article  CAS  PubMed  Google Scholar 

  11. Smith-Norowitz TA, Chotikanatis K, Erstein DP et al (2016) Chlamydia pneumoniae enhances the Th2 profile of stimulated peripheral blood mononuclear cells from asthmatic patients. Hum Immunol 77:382–388

    Article  CAS  PubMed  Google Scholar 

  12. Willis-Karp M (2001) IL-12/IL-13 in allergic asthma. J Allergy Clin Immunol 107:9–18

    Article  Google Scholar 

  13. Cowen MK, Wakefield DB, Cloutier MM (2007) Classifying asthma severity: objective versus subjective measures. J Asthma 44:711–715

    Article  PubMed  Google Scholar 

  14. EPR-3 (2007) Expert panel report 3: guidelines for the diagnosis and management of asthma (EPR-3 2007). US Department of Health and Human Services; National Institutes of Health; National Heart, Lung, and Blood Institute; National Asthma Education and Prevention Program :40–43. http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf

  15. Wang SP, Grayston JT (1986) Microimmunofluorescence serological studies with the TWAR organism. In: Oriel D, Ridgeway G (eds) Chlamydial infections: proceedings of the sixth international symposium on human chlamydial infections. Cambridge University Press, Cambridge, pp 329–332

    Google Scholar 

  16. Roblin PM, Dumornay W, Hammerschlag MR (1992) Use of HEp-2 cells for improved isolation and passage of Chlamydia pneumoniae. J Clin Microbiol 1992(30):1968–1971

    Google Scholar 

  17. Apfalter P, Barousch W, Nehr M et al (2003) Comparison of a new quantitative ompA-based real-time PCR TaqMan assay for detection of Chlamydia pneumoniae DNA in respiratory specimens with four conventional PCR assays. J Clin Microbiol 41:592–600

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Dzhindzhikhashvili MS, Joks R, Smith-Norowitz TA et al (2013) Doxycycline suppresses Chlamydia pneumoniae-mediated increases in ongoing immunoglobulin E and interleukin-4 responses by peripheral blood mononuclear cells of patients with allergic asthma. J Antimicrob Chemother 68:2363–2368

    CAS  PubMed  Google Scholar 

  19. Wissel H, Schulz C, Koehne P et al (2005) Chlamydophila pneumoniae induces expression of Toll-like Receptor 4 and release of TNF-α and MIP-2 via an NF-κβ pathway in rat type II pneumocytes. Respir Res 6:51

    Article  PubMed  PubMed Central  Google Scholar 

  20. Heinemann M, Susa M, Simnacher U, Marre R, Essig A (1996) Growth of Chlamydia pneumoniae induces cytokine production and expression of CD14 in a human monocytic cell line. Infect Immun 64:4872–4875

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Kaukoranta-Tolvanen SS, Ronni T, Leinonen M, Saikku P, Laitinen K (1996) Expression of adhesion molecules on endothelial cells stimulated by Chlamydia pneumoniae. Microb Pathog 21:407–411

    Article  CAS  PubMed  Google Scholar 

  22. Pentilla JM, Anttila M, Puolakkainen M et al (1998) Local immune responses to Chlamydia pneumoniae in the lungs of BALB/c mice during primary infection and reinfection. Infect Immun 66:5113–5118

    Google Scholar 

  23. Geng Y, Berencsi K, Gyulai Z et al (2000) Roles of interleukin-12 and gamma interferon in murine Chlamydia pneumoniae infection. Infect Immun 68:2245–2253

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Orgun NN, Mathis MA, Wilson CB, Way SS (2008) Deviation from a strong Th1-dominated to a modest Th17-dominated CD4 T cell response in the absence of IL-12p40 and type I IFNs sustains protective CD8 T cells. J Immunol 180:4109–4115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Prebeck S, Kirschning C, Durr S et al (2001) Predominant role of toll-like receptor 2 versus 4 in Chlamydia pneumoniae-induced activation of dendritic cells. J Immunol 167:3316–3323

    Article  CAS  PubMed  Google Scholar 

  26. Bulut Y, Faure E, Thomas L et al (2002) Chlamydial heat shock protein 60 activates macrophages and endothelial cells through Toll-like receptor 4 and MD2 in a MyD88-dependent pathway. J Immunol 168:1435–1440

    Article  CAS  PubMed  Google Scholar 

  27. Costa CP, Kirschning CJ, Busch D et al (2002) Role of chlamydial heat shock protein 60 in the stimulation of innate immune cells by Chlamydia pneumoniae. Eur J Immunol 32:2460–2470

    Article  PubMed  Google Scholar 

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Acknowledgements

We would like to thank Kevin B. Norowitz, M.D., Department of Pediatrics, SUNY Downstate Medical Center for fruitful discussions.

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Authors and Affiliations

  1. Division of Infectious Diseases, Department of Pediatrics, State University of New York Downstate Medical Center, Box 49, 450 Clarkson Ave., Brooklyn, NY, 11203, USA

    T. A. Smith-Norowitz, J. Perlman, Y. M. Norowitz, M. R. Hammerschlag & S. Kohlhoff

  2. Department of Medicine, State University of New York Downstate Medical Center, Brooklyn, NY, 11203, USA

    R. Joks

  3. Department of Pathology, State University of New York Downstate Medical Center, Brooklyn, NY, 11203, USA

    H. G. Durkin

Authors
  1. T. A. Smith-Norowitz
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  2. J. Perlman
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  3. Y. M. Norowitz
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  4. R. Joks
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  5. H. G. Durkin
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  6. M. R. Hammerschlag
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  7. S. Kohlhoff
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Corresponding author

Correspondence to T. A. Smith-Norowitz.

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Conflict of interest

The authors declare no conflict of interest to disclose.

Human and animal rights statement

Research involving human participants was approved by the SUNY Downstate Med Ctr IRB committee (stated in methods).

Informed consent

We had informed consent from patients.

Funding

This work was supported by the Thrasher Research Fund (Young Investigator Award awarded to Stephan Kohlhoff, M.D.) and a NY State Divisional Grant (Awarded to Tamar A. Smith-Norowitz, Ph.D).

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Smith-Norowitz, T.A., Perlman, J., Norowitz, Y.M. et al. Chlamydia pneumoniae induces interleukin-12 responses in peripheral blood mononuclear cells in asthma and the role of toll like receptor 2 versus 4: a pilot study. Ir J Med Sci 186, 511–517 (2017). https://doi.org/10.1007/s11845-016-1549-9

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  • DOI: https://doi.org/10.1007/s11845-016-1549-9

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