Herpesvirus seropositivity in childhood associates with decreased monocyte-induced NK cell IFN-gamma production.
EBV infection is inversely associated with IgE sensitization in children, and this association is further enhanced by CMV coinfection. In mice, herpesvirus latency causes systemic innate activation and protection from bacterial coinfection, implying the importance of herpesviruses in skewing immune responses during latent infection. Early control of viral infections depends on IFN-gamma release by NK cells, which generally requires the presence of accessory cells. We investigated IFN-gamma production by NK cells in PBMCs from children seropositive (SP) for EBV alone, for both EBV and CMV, or seronegative for both viruses. The ability of classical (CD14(++)CD16(-)) and proinflammatory (CD14(+)CD16(+)) monocytes to induce autologous NK cell IFN-gamma was studied by coculture experiments with enriched CD3(-)CD56(+) cells. Transwell experiments were used to evaluate how monocytes interact with NK cells to induce IFN-gamma synthesis. SP children had a significantly reduced proportion of IFN-gamma(+) NK cells and cognate intracellular IFN-gamma levels, which was more pronounced in CMV-coinfected subjects. Also, resting PBMCs of SP children displayed lower proportions of proinflammatory monocytes. IFN-gamma production by NK cells was dependent on interactions with monocytes, with the proinflammatory subset inducing the highest IFN-gamma. Finally, SP children had markedly lower levels of plasma IFN-gamma, concurrent with in vitro findings. Herpesvirus infections could be one contributing factor for maturation toward balanced Th1-Th2 responses. Our data indicate that early infection by herpesviruses may affect NK cell and monocyte interactions and thereby also influence the development of allergies.
Saghafian-Hedengren
Shanie
S
Department of Immunology, Wenner-Gren Institute, Stockholm University, Stockholm, Sweden. shanie@imun.su.se
Sundström
Yvonne
Y
Sohlberg
Ebba
E
Nilsson
Caroline
C
Linde
Annika
A
Troye-Blomberg
Marita
M
Berg
Louise
L
Sverremark-Ekström
Eva
E
D002675:Child, Preschool; D018920:Coculture Techniques; D016207:Cytokines / Q000276:immunology; D003587:Cytomegalovirus / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006566:Herpesviridae Infections / Q000276:immunology*; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000821:virology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D009000:Monocytes / Q000276:immunology* / Q000821:virology
D016207:Cytokines; D007371:Interferon-gamma