Cytokine and nitric oxide production by mouse macrophages infected with brazilian flaviviruses

Abstract

The Flaviviridae family, Flavivirus genus includes viruses that are transmitted to vertebrates by infected mosquitoes or ticks. The genus Flavivirus includes a variety of viruses that cause diseases such as acute febrile illness, encephalitis, and hemorrhagic fever. Flaviviruses primarily infect blood monocytes and tissue macrophages, which have been shown to be permissive, supporting viral replication and serving as virus reservoirs. On the other hand, these cells may have an important antiviral activity related to modulation by cytokine production and by the capacity of these cells to synthesize reactive free radicals such as nitric oxide (NO) which can have a microbicidal effect. The present study was performed in order to determine the production of cytokines interleukin-1beta (IL-1β), tumor necrosis factor -alpha (TNF-α), transforming growth factor- beta (TGF-β) and interferon -alpha (IFN-α) and NO by macrophages infected with one of four Brazilian flaviviruses, Bussuquara virus (BUSV), Yellow Fever virus (YFV), Rocio virus (ROCV) and Encephalitis Saint Louis virus (SLEV), and to verify the possible antiviral effect of NO during macrophage infection with ROCV. Moreover, we asked if the different viruses were able to regulate bacterial lipopolysaccharide (LPS) induced cytokine production. Our results showed that YFV and SLEV reduced the production of IL-1β and TGF-β by LPS-stimulated macrophages, while ROCV only diminished LPS-stimulated TGF-β synthesis. On the other hand, BUSV more likely favored an enhancement of the LPS-induced production of IL-1β by macrophages. Additionally, while most of the viruses stimulated the production of IFN-α, none of them altered the production of TNF-α by murine macrophages. Interestingly, all viruses induced synthesis of NO that was not correlated with antiviral activity for ROCV.

Bovine viral diarrhea virus type 2 in vivo infection modulates TLR4 responsiveness in differentiated myeloid cells which is associated with decreased MyD88 expression

“…Given that proinflammatory cytokine production can be induced via several signaling pathways, it is plausible that not all are affected in the same manner. Nonetheless, these results, along with those in previous studies (Barros et al, 2009;Chung et al, 2011;Liu et al, 2011), suggest that in vitro-derived terminally differentiated macrophages generally have a decreased proinflammatory cytokine mRNA profile and a reduced ability to respond to TLR4 ligation following infection with Flaviviridae.…”

“…TLR hyporesponsiveness has been demonstrated in PBMCs isolated from chronically infected HCV patients which correlated to more severe disease and worse clinical outcome (Chung et al, 2011;Liu et al, 2011). Yellow fever virus and St. Louis encephalitis virus infection reduced IL-1␤ levels in LPS-stimulated MDM compared to uninfected control cells (Barros et al, 2009). We found that M derived during BVDV2 infection generally have reduced inflammatory cytokine mRNA.…”

Minocycline differentially modulates macrophage mediated peripheral immune response following Japanese encephalitis virus infection

“…The mechanism of evasion of host immune system by JEV is a matter of concern because once the virus reaches the CNS, it replicates at an accelerated rate, and thereby causes irreparable damage that often leads to fatality. JEV (Aleyas et al, 2009) and other flaviviruses (Barros et al, 2009;Rios et al, 2006) has been shown to infect monocyte-macrophages and replicate quite efficiently in them for long time periods (Rios et al, 2006). We had earlier observed that in a mice model of Japanese encephalitis, peripheral inflammatory cells containing the virus, migrates into the brain during acute stages (data not shown).…”

Influence of the CCR-5/MIP-1 α Axis in the Pathogenesis of Rocio Virus Encephalitis in a Mouse Model

“…26 In addition to the antiviral effect of nitric oxide, this free radical can induce septic shock, mainly by extensive smooth muscle relaxation, which results in low blood pressure. 27 Our group also reported the ability of ROCV to induce apoptosis in neurons, which caused neuronal death.…”