Variation in inflammatory/regulatory cytokines in secondary, tertiary, and quaternary challenges with dengue virus.
Secondary heterologous dengue infection is a risk factor for severe disease manifestations because of the immune-enhancement phenomenon. Succeeding clinical infections are seldom reported, and the clinical course of tertiary and quaternary dengue infections is not clear. Cuba represents a unique environment to study tertiary/quaternary dengue infections in a population with known clinical and serologic dengue markers and no dengue endemicity. We took advantage of this exceptional epidemiologic condition to study the effect of primary, secondary, tertiary, and quaternary dengue infection exposure on the expression of pro-inflammatory and regulatory cytokines, critical in dengue infection pathogenesis, by using a dengue infection ex vivo model. Whereas secondary exposure induced a high cytokine response, we found a significantly lower expression of tumor necrosis factor-α, interferon-γ, interleukin-10, and tumor growth factor-β after tertiary and quaternary infectious challenge. Significant differences in expression of the cytokines were seen between the dengue immune profiles, suggesting that the sequence in which the immune system encounters serotypes may be important in determining the nature of the immune response to subsequent infections.
Department of Virology, Tropical Medicine Institute Pedro Kourí, Havana, Cuba. siebet@ipk.sld.cu
Beatriz
B
Sierra
Ana B
AB
Pérez
Mayling
M
Alvarez
Gissel
G
García
Katrin
K
Vogt
Eglys
E
Aguirre
Kathrin
K
Schmolke
Hans-Dieter
HD
Volk
María G
MG
Guzmán
D000293:Adolescent; D000328:Adult; D057134:Antibodies, Neutralizing / Q000097:blood; D000956:Antigens, Viral / Q000276:immunology; D003462:Cuba; D003715:Dengue / Q000097:blood* / Q000276:immunology; D003716:Dengue Virus / Q000145:classification / Q000276:immunology*; D016021:Epidemiologic Studies; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000276:immunology; D007371:Interferon-gamma / Q000097:blood*; D016753:Interleukin-10 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009500:Neutralization Tests; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000097:blood*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*; D055815:Young Adult
D057134:Antibodies, Neutralizing; D000956:Antigens, Viral; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma