Pregnant women infected with pandemic influenza A(H1N1)pdm09 virus showed differential immune response correlated with disease severity.
BACKGROUND
During pregnancy, immunological and hormonal alterations place women at increased risk for influenza-related severe illnesses including hospitalization and death. Although A(H1N1) pdm09 infection resulted in increased disease severity in pregnant women, the precise mechanisms responsible for this risk have yet to be established.


OBJECTIVE
The present study was aimed to investigate the role of host chemokines and cytokine profiles in A(H1N1) pdm09 infection regarding disease severity in pregnant women.


METHODS
This retrospective survey examined 41 pregnant women with confirmed A(H1N1) pdm09 infection. Of them, 12 died (D), 29 survived (S), and 17 remained uninfected and served as controls (C). Antiviral response was evaluated for IFN-β expression and gene expression profiles of cytokines (TNF-α, IL-6, IL-12, TGF-β) and chemokines (IL-8, RANTES, MCP-1, IP-10), and the viral Matrix (M1) gene was quantified and normalized using the housekeeping gene product β-actin mRNA.


RESULTS
Higher IL-8 and TNF-α mRNA expression were found in D and S compared with C, while IL-6 showed higher expression in D. Interestingly, these results were associated with a decrease in the anti-inflammatory response of TGF-β mRNA and IFN-β. These alterations would lead to an imbalance in the immune response of those patients.


CONCLUSIONS
Pregnancy-related reductions in IFN-β and TGF-β expression levels and elevated levels of pro-inflammatory cytokines could explain the increased severity of infection and death of pregnant women. These findings may help improve the understanding of the high susceptibility and disease severity to influenza virus infection during pregnancy.
National Influenza Centre PAHO/WHO, Laboratorio Nacional de Referencia de Influenza y Virus Respiratorios, Servicio Virosis Respiratorias, Departamento Virología, Instituto Nacional de Enfermedades Infecciosas, ANLIS "Carlos G. Malbrán", Buenos Aires, Argentina. Electronic address: nperiolo@anlis.gov.ar.
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Periolo
National Influenza Centre PAHO/WHO, Laboratorio Nacional de Referencia de Influenza y Virus Respiratorios, Servicio Virosis Respiratorias, Departamento Virología, Instituto Nacional de Enfermedades Infecciosas, ANLIS "Carlos G. Malbrán", Buenos Aires, Argentina.
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Avaro
National Influenza Centre PAHO/WHO, Laboratorio Nacional de Referencia de Influenza y Virus Respiratorios, Servicio Virosis Respiratorias, Departamento Virología, Instituto Nacional de Enfermedades Infecciosas, ANLIS "Carlos G. Malbrán", Buenos Aires, Argentina.
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Czech
National Influenza Centre PAHO/WHO, Laboratorio Nacional de Referencia de Influenza y Virus Respiratorios, Servicio Virosis Respiratorias, Departamento Virología, Instituto Nacional de Enfermedades Infecciosas, ANLIS "Carlos G. Malbrán", Buenos Aires, Argentina.
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Russo
National Influenza Centre PAHO/WHO, Laboratorio Nacional de Referencia de Influenza y Virus Respiratorios, Servicio Virosis Respiratorias, Departamento Virología, Instituto Nacional de Enfermedades Infecciosas, ANLIS "Carlos G. Malbrán", Buenos Aires, Argentina.
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Benedetti
National Influenza Centre PAHO/WHO, Laboratorio Nacional de Referencia de Influenza y Virus Respiratorios, Servicio Virosis Respiratorias, Departamento Virología, Instituto Nacional de Enfermedades Infecciosas, ANLIS "Carlos G. Malbrán", Buenos Aires, Argentina.
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Pontoriero
National Influenza Centre PAHO/WHO, Laboratorio Nacional de Referencia de Influenza y Virus Respiratorios, Servicio Virosis Respiratorias, Departamento Virología, Instituto Nacional de Enfermedades Infecciosas, ANLIS "Carlos G. Malbrán", Buenos Aires, Argentina.
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Campos
Instituto de Microbiología y Parasitología Médica, Universidad de Buenos Aires-Consejo Nacional de Investigaciones Científicas y Tecnológicas (IMPaM, UBA CONICET), Argentina.
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Peralta
National Influenza Centre PAHO/WHO, Laboratorio Nacional de Referencia de Influenza y Virus Respiratorios, Servicio Virosis Respiratorias, Departamento Virología, Instituto Nacional de Enfermedades Infecciosas, ANLIS "Carlos G. Malbrán", Buenos Aires, Argentina.
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Baumeister
D000328:Adult; D018925:Chemokines / Q000235:genetics* / Q000276:immunology / Q000302:isolation & purification; D016207:Cytokines / Q000235:genetics* / Q000276:immunology / Q000302:isolation & purification; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology* / Q000401:mortality / Q000821:virology; D016899:Interferon-beta / Q000235:genetics / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D016209:Interleukin-8 / Q000235:genetics / Q000276:immunology; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology* / Q000401:mortality; D012189:Retrospective Studies; D012720:Severity of Illness Index; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D018925:Chemokines; D016207:Cytokines; D015850:Interleukin-6; D016209:Interleukin-8; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016899:Interferon-beta
A(H1N1)pdm09; Chemokines; Cytokines; Influenza virus; Pregnant women