Macrophages and cytokines in the early defence against herpes simplex virus

Abstract

Herpes simplex virus (HSV) type 1 and 2 are old viruses, with a history of evolution shared with humans. Thus, it is generally well-adapted viruses, infecting many of us without doing much harm, and with the capacity to hide in our neurons for life. In rare situations, however, the primary infection becomes generalized or involves the brain.Normally, the primary HSV infection is asymptomatic, and a crucial element in the early restriction of virus replication and thus avoidance of symptoms from the infection is the concerted action of different arms of the innate immune response. An early and light struggle inhibiting some HSV replication will spare the host from the real war against huge amounts of virus later in infection. As far as such a war will jeopardize the life of the host, it will be in both interests, including the virus, to settle the conflict amicably. Some important weapons of the unspecific defence and the early strikes and beginning battle during the first days of a HSV infection are discussed in this review.Generally, macrophages are orchestrating a multitude of anti-herpetic actions during the first hours of the attack. In a first wave of responses, cytokines, primarily type I interferons (IFN) and tumour necrosis factor are produced and exert a direct antiviral effect and activate the macrophages themselves. In the next wave, interleukin (IL)-12 together with the above and other cytokines induce production of IFN-γ in mainly NK cells. Many positive feed-back mechanisms and synergistic interactions intensify these systems and give rise to heavy antiviral weapons such as reactive oxygen species and nitric oxide. This results in the generation of an alliance against the viral enemy.However, these heavy weapons have to be controlled to avoid too much harm to the host. By IL-4 and others, these reactions are hampered, but they are still allowed in foci of HSV replication, thus focusing the activity to only relevant sites. So, no hero does it alone. Rather, an alliance of cytokines, macrophages and other cells seems to play a central role. Implications of this for future treatment modalities are shortly considered.

In vitro and in vivo immunomodulatory activity of sulfated polysaccharides from Enteromorpha prolifera

“…4), the F 1 and F 2 fractions resulted in considerable mRNA expression of these cytokines, whereas relatively little mRNA expression was observed with the F 3 fraction. In general, pro-inflammatory mediators such as TNF-␣, IL-1␤, IL-6 and PGE 2 are essential for host survival from injured and/or abnormal [14,20,21]. These cytokines could be produced by the stimulation of immune cells, including T-cells, B-cells and macrophages.…”

Functional activity of peritoneal macrophages from sensitive and resistant mouse strains during intravaginal infection with herpes simplex virus type 2 and mucosal vaccination

“…Published data show that interferon-α (IFN-α) is also involved in the early nonspecific defense response to herpes infection [8]. As compared to sensitive mice, resistant animals are characterized by earlier activation of IFN-α (after 2 h) and autocrine IFN-α/β-regulated respiratory burst [4]. It should be emphasized that the increase in IFN-α/β activity depends on activation of the intracellular receptor TLR9.…”

“…This process is determined by various components of the innate immune response [3,5]. Macrophages produce an antiviral effect on HSV within the first hours after infection [4]. It should be emphasized that HSV is an intracellular pathogen, and macrophages can phagocytize HSV.…”

Fulminant Hepatic Failure in a Patient with Crohn’s Disease on Infliximab Possibly Related to Reactivation of Herpes Simplex Virus 2 Infection

“…Overall, HBV reactivation is much more common [23, 24] and this is thought to be due to the required involvement of TNF α in the host immune response to HBV infection [25, 26]. Similarly, the role of TNF α in host defense mechanisms against the herpes simplex virus is thought to be important and likely involves macrophage activation and immune cell signalling [27]. Mouse models have demonstrated that TNF α depletion leads to rapid reactivation of HSV-1 infections and TNF α knockout mice are more susceptible to primary HSV-1 infection and had higher subsequent rates of mortality [28].…”