Induction of interferon alpha from human lymphocytes by autologous, dengue virus-infected monocytes.
Human monocytes actively replicate dengue virus. To dissect the primary immune responses to dengue virus-infected monocytes (DV-monocytes), we analyzed the interaction between autologous DV-monocytes and the peripheral blood lymphocytes (PBL) of dengue nonimmune donors. Interferon (IFN) activity was detected when PBL were cultured with DV-monocytes. Cell contact between PBL and DV-monocytes was required for IFN production; however, MHC compatibility between PBL and monocytes was not necessary. DV-monocytes fixed with paraformaldehyde or glutaraldehyde, which produced no infectious virus, also induced high levels of IFN from PBL. The ability of DV-monocytes to induce IFN correlated with the appearance of dengue antigens. The PBL that produce IFN were characterized by FACS sorting using monoclonal and polyclonal antibodies. HLA-DR+ and T3- cells produced high titers of IFN, while HLA-DR- and T3+ cells produced very low or undetectable levels of IFN. Moderate titers of IFN were produced by cells contained in B cell fractions (surface immunoglobulin-positive, B1+, and Leu-12+), and cells contained in natural killer cell fractions (Leu-11+ and OKM1+). Therefore, IFN-producing cells are heterogeneous, and the predominant producer cells are characterized as HLA-DR+ and non-T lymphocytes. The IFN produced was characterized by RIA using mAbs to IFN-alpha and IFN-gamma. The IFN-alpha was the predominant IFN produced; in addition, a low level of IFN-gamma was also detected in some experiments. The culture fluids obtained from PBL exposed to autologous DV-monocytes, which contained high IFN activity, completely inhibited dengue virus infection of monocytes. These results suggest that IFN-alpha produced by PBL exposed to DV-monocytes may play an important role in controlling primary dengue virus infection.
D000911:Antibodies, Monoclonal; D000917:Antibody Formation; D002450:Cell Communication; D003609:Dactinomycin / Q000494:pharmacology; D003715:Dengue / Q000097:blood*; D003716:Dengue Virus; D005557:Formaldehyde / Q000494:pharmacology; D005976:Glutaral / Q000494:pharmacology; D006801:Humans; D007370:Interferon Type I / Q000096:biosynthesis*; D008214:Lymphocytes / Q000378:metabolism*; D009000:Monocytes / Q000382:microbiology*; D011108:Polymers / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D007370:Interferon Type I; D011108:Polymers; D003609:Dactinomycin; D005557:Formaldehyde; D005976:Glutaral; C003043:paraform