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Chemokine Expression Patterns in the Systemic and Genital Tract Compartments are Associated with HIV-1 Infection in Women from Benin

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Abstract

Introduction

Understanding the genital mucosal immunity and the factors involved in linking innate to adaptive immunity is crucial for the design of efficient preventive strategies against human immunodeficiency virus (HIV)-1.

Methods

Levels of both genital mucosal and blood chemokines were compared between 58 HIV-1-uninfected and 50 HIV-1-infected female commercial sex workers (CSWs) as well as 53 HIV-1-uninfected non-CSW control women at low risk for exposure, recruited in Cotonou, Benin.

Results

HIV-1-infected CSWs had significantly higher blood and genital levels of monocyte chemotactic protein (MCP-3/CCL7) and monokine induced by gamma interferon (MIG/CXCL9) compared with those in both the HIV-1-uninfected CSW and non-CSW groups. In the HIV-1-infected group, levels of MCP-3 and MIG were significantly higher in the genital mucosa than in the blood. However, the blood levels of macrophage inflammatory protein (MIP-1a/CCL3) and MIP-1b/CCL4 were higher in HIV-1-uninfected CSWs compared with those in the other groups.

Conclusion

Increased production of chemokines in the genital tract may favour the recruitment of HIV-1 target cells causing a mucosal environment that promotes viral replication and dissemination, whereas higher expression of β-chemokines at the systemic level is associated with protection from HIV-1 infection.

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References

  1. Haynes BF, Shattock RJ. Critical issues in mucosal immunity for HIV-1 vaccine development. J Allergy Clin Immunol. 2008;122:3–9.

    Article  CAS  PubMed  Google Scholar 

  2. Padian NS, van der Straten A, Ramjee G, Chipato T, de Bruyn G, Blanchard K, et al. Diaphragm and lubricant gel for prevention of HIV acquisition in Southern African women: a randomised controlled trial. Lancet. 2007;370:251–61.

    Article  PubMed  Google Scholar 

  3. Hel Z, McGhee JR, Mestecky J. HIV infection: first battle decides the war. Trends Immunol. 2006;27:274–81.

    Article  CAS  PubMed  Google Scholar 

  4. Glass WG, Rosenberg HF, Murphy PM. Chemokine regulation of inflammation during acute viral infection. Curr Opin Allergy Clin Immunol. 2003;3:467–73.

    Article  CAS  PubMed  Google Scholar 

  5. Colobran R, Adreani P, Ashhab Y, Llano A, Esté JA, Dominguez O, et al. Multiple products derived from two CCL4 loci: high incidence of a new polymorphism in HIV positive patients. J Immunol. 2005;174:5655–64.

    CAS  PubMed  Google Scholar 

  6. Gonzalez E, Kulkarni H, Bolivar H, Mangano A, Sanchez R, Catano G, et al. The influence of CCL3L1 gene-containing segmental duplications on HIV-1/AIDS susceptibility. Science. 2005;307:1434–40.

    Article  CAS  PubMed  Google Scholar 

  7. Iqbal SM, Ball TB, Kimani J, Thottingal P, Embree JE, Fowke KR, et al. Elevated T cell counts and RANTES expression in the genital mucosa of HIV-1-resistant Kenyan commercial sex workers. J Infect Dis. 2005;192:728–38.

    Article  CAS  PubMed  Google Scholar 

  8. Hirbod T, Nilsson J, Andersson S, Uberti-Foppa C, Ferrari D, Maghi M, et al. Upregulation of interferon-α and RANTES in the cervix of HIV-1 seronegative women with high-risk behavior. J Acquir Immune Defic Syndr. 2006;43:137–43.

    Article  CAS  PubMed  Google Scholar 

  9. Kaul R, Rebbapragada A, Hirbod T, Wachihi C, Ball TB, Plummer FA, et al. Genital levels of soluble immune factors with anti-HIV activity may correlate with increased HIV susceptibility. AIDS. 2008;22:2049–51.

    Article  PubMed  Google Scholar 

  10. Campbell GR, Spector SA. CCL2 increases X4-tropic HIV-1 entry into resting CD4+ T Cells. J Biol Chem. 2008;283:30745–53.

    Article  CAS  PubMed  Google Scholar 

  11. Brainard DM, Tager AM, Misdraji J, Frahm N, Lichterfeld M, Draeneret R, et al. Decreased CXCR3+ CD8 T cells in advanced human immunodeficiency virus infection suggest that a homing defect contributes to cytotoxic T-lymphocyte dysfunction. J Virol. 2007;81:8439–50.

    Article  CAS  PubMed  Google Scholar 

  12. Lajoie J, Poudrier J, Massinga-Loembe M, Guédou F, Agossa-Gbenafa C, Labbé AC, et al. Differences in immunoregulatory cytokine expression patterns in the systemic and genital tract compartments of HIV-1 infected commercial sex workers in Benin. Mucosal Immunol. 2008;1:309–16.

    Article  CAS  PubMed  Google Scholar 

  13. Gumbi PP, Nkwanyana NN, Bere A, Burgers WA, Gray CM, Williamson AC, et al. Impact of inflammation on cervical human immunodeficiency virus (HIV-1)-specific DC8 T-cell responses in the female genital tract during chronic HIV infection. J Virol. 2008;82:8529–36.

    Article  CAS  PubMed  Google Scholar 

  14. Wira CR, Fahey JV, Sentman CL, Pioli PA, Shen L. Innate and adaptive immunity in female genital tract: cellular responses and interactions. Immunol Rev. 2005;206:306–35.

    Article  PubMed  Google Scholar 

  15. Sugaya M, Loré K, Koup RA, Douek DC, Blauvelt A. HIV-infected Langerhans cells preferentially transmit virus to proliferating autologous CD4+ memory t cells located within Langerhans Cell-T cell clusters. J Immunol. 2004;172:2219–24.

    CAS  PubMed  Google Scholar 

  16. Sharkey DJ, Macpherson AM, Tremellen KP, Robertson SA. Seminal plasma differentially regulates inflammatory cytokine gene expression in human cervical and vaginal epithelial cells. Mol Hum Reprod. 2007;13:491–501.

    Article  CAS  PubMed  Google Scholar 

  17. Cohen CR, Plummer FA, Mugo N, Maclean L, Shen C, Bukosi EA, et al. Increased interleukin-10 in the endocervical secretions of women with non-ulcerative sexually transmitted diseases: a mechanism for enhanced HIV-1 transmission? AIDS. 1999;13:327–32.

    Article  CAS  PubMed  Google Scholar 

  18. Boulton IC, Gray-Owen SD. Neisserial binding to CEACAM-1 arrests the activation and proliferation of CD4+ T lymphocytes. Nat Immunol. 2002;3:229–36.

    Article  CAS  PubMed  Google Scholar 

  19. Fichorova RN, Desai PJ, Gibson FC, Genco CA. Distinct proinflammatory host responses to Neisseria Gonorrhoeae infection in immortalized human cervical and vaginal epithelial cells. Infect Immun. 2001;69:5840–8.

    Article  CAS  PubMed  Google Scholar 

  20. Freeman EE, Weiss HA, Glynn JR, Cross PL, Whitworth JA, Hayes RJ. Herpes simplex virus 2 infection increases HIV acquisition in men and women: systematic review and meta-analysis of longitudinal studies. AIDS. 2006;20:73–83.

    Article  PubMed  Google Scholar 

  21. Rebbapragada A, Wachihi C, Pettengell C, Sunderji S, Huibner S, Jaoko W, et al. Negative mucosal synergy between herpes simplex type 2 and HIV in the female genital tract. AIDS. 2007;21:589–98.

    Article  PubMed  Google Scholar 

  22. Kaul R, Plummer FA, Kimani J, Dong T, Kiama P, Rostron T, et al. HIV-1-specific mucosal CD8+ lymphocyte responses in the cervix of HIV-1-resistant prostitutes in Nairobi. J Immunol. 2000;164:1602–11.

    CAS  PubMed  Google Scholar 

  23. Kaul R, Trabattoni D, Bwayo JJ, Arienti D, Zagliani A, Mwanji FM, et al. HIV-1-specific mucosal IgA in a cohort of HIV-1-resistant Kenyan sex workers. AIDS. 1999;13:23–9.

    Article  CAS  PubMed  Google Scholar 

  24. Devito C, Hinkula J, Kaul R, Kimani J, Kiama P, Lopalco L, et al. Cross-clade HIV-1-specific neutralizing IgA in mucosal and systemic compartments of HIV-1-exposed, persistently seronegative subjects. J Acquir Immune Defic Syndr. 2002;30:413–20.

    CAS  PubMed  Google Scholar 

  25. Suresh P, Wanchu A, Bhatnagar A, Sachdeva RK, Sharma M. Spontaneous and antigen-induced chemokine production in exposed but uninfected partners of HIV type 1-infected individuals in North India. AIDS Res Hum Retroviruses. 2007;23:261–8.

    Article  CAS  PubMed  Google Scholar 

  26. Schall TJ, Bacon K, Camp RD, Kaspari JW, Goeddel DV. Human macrophage inflammatory protein alpha (MIP-1 alpha) and MIP-1 beta chemokines attract distinct populations of lymphocytes. J Exp Med. 1993;177:1821–6.

    Article  CAS  PubMed  Google Scholar 

  27. Lillard JW, Singh UP, Boyaka PN, Singh S, Taub DD, McGhee JR. MIP-1 alpha and MIP-1 beta differentially mediate mucosal and systemic adaptive immunity. Blood. 2003;101:807–14.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by grant HOP-79213 from the Canadian Institutes of Health Research (CIHR) and by the Réseau SIDA from the Fonds de la Recherche en Santé du Québec (FRSQ). Julie Lajoie and Marguerite Massinga Loembe hold Student Research awards from the CIHR. Marguerite Massinga Loembe additionally held a fellowship from the AUF (Agence Universitaire de la Francophonie). Michel Alary and Michel Roger are recipients of Research Scholar awards from the FRSQ. We are indebted to Nassirou Geraldo, Aina Gabin, Carmelle Assogba and Clémence Agossa-Gbenafa for their clinical expertise, to Gérard Ahotin, Laurette Djossou and Ella Goma for their technical assistance and to Georges Batona and other field workers who helped with recruitment of CSWs.

Authors' contribution

M. Roger is the lead investigator of this study and with J. Lajoie and J. Poudrier, designed the experiments, performed the analysis and wrote the manuscript. J. Lajoie performed the experiments. M. Massinga Loembe, A-C Labbé, F. Guédou and M. Alary were responsible for the participants' recruitment and provided clinical and laboratory data. M. Massinga Loembe and F Leblond were responsible for the sample processing and data collection. All authors edited and approved the final version of the manuscript.

Conflicts of interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. Laboratoire d’immunogénétique, Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), Montreal, Canada

    Julie Lajoie, Johanne Poudrier & Michel Roger

  2. Département de Microbiologie et Immunologie, Hôpital Notre-Dame du Centre Hospitalier de l’Université de Montréal (CHUM), 1560 Sherbrooke Est, Montréal, QC, H2L 4M1, Canada

    Julie Lajoie, Johanne Poudrier & Michel Roger

  3. Laboratory of Immunology, Institute of Tropical Medicine, Antwerp, Belgium

    Marguerite Massinga Loembe

  4. Unité de Recherche en Santé des Populations, Centre hospitalier affilié universitaire de Québec and Université Laval, Québec, Canada

    Marguerite Massinga Loembe, Fernand Guédou & Michel Alary

  5. Département de Microbiologie de l’hôpital Maisonneuve-Rosemont, Montréal, Canada

    François Leblond & Annie-Claude Labbé

Authors
  1. Julie Lajoie
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  2. Johanne Poudrier
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  3. Marguerite Massinga Loembe
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  4. Fernand Guédou
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  6. Annie-Claude Labbé
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  7. Michel Alary
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  8. Michel Roger
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Corresponding author

Correspondence to Michel Roger.

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Lajoie, J., Poudrier, J., Massinga Loembe, M. et al. Chemokine Expression Patterns in the Systemic and Genital Tract Compartments are Associated with HIV-1 Infection in Women from Benin. J Clin Immunol 30, 90–98 (2010). https://doi.org/10.1007/s10875-009-9343-3

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  • DOI: https://doi.org/10.1007/s10875-009-9343-3

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