Role of Macrophages in Acute Murine Cytomegalovirus Infection

Abstract

It has been recognized that macrophages play an important role in controlling virus infection in experimental animal models. To evaluate the role of macrophages in acute murine cytomegalovirus infection, macrophages in the spleen and the liver were eliminated by an intravenous injection of liposomes containing a cytolytic agent, dichloromethylene diphosphonate. The depletion of macrophages led to a significant increase of virus titer in the spleen and lungs in both susceptible BALB/c and resistant C57BL/6 mice during the first three days after intravenous infection. In the spleen, the increase of virus titer in macrophagedepleted BALB/c mice was much greater than that in NK cell-depleted mice. These results suggest that macrophages contribute to protection mainly by the mechanisms which are independent of NK cells during the first three days after infection. The increase of virus titer in macrophage-depleted C57BL/6 mice was as great as that in NK cell-depleted mice because of the high contribution of NK cells to protection in C57BL/6 mice. In the liver in both strains of mice, the effects of macrophage depletion on virus titer were not as much as those in the spleen and lungs. Furthermore, the local depletion of peritoneal macrophages resulted in a great increase of virus titer in the spleen at three days after intraperitoneal infection. We conclude that macrophages greatly contribute to decreasing the virus load in some organs possibly through either or both intrinsic and extrinsic mechanisms in the early phase of primary infection with murine cytomegalovirus.

Role of Nitric Oxide Synthase Type 2 in Acute Infection with Murine Cytomegalovirus

“…Hanson (46) recently reported that the proficiency of MCMV replication in macrophages themselves positively correlates with virulence in vivo. Indeed, macrophages, a dominant source of NOS2-derived NO, play a protective role against MCMV infection by the expression of the intrinsic antiviral activity (6,45). These findings show the possibility that the absence of NOS2-mediated antiviral activity of macrophages may enhance the viral replication in these cells, hence severe virusinduced pathogenicity.…”

“…This result implied that NOS2-associated antiviral activity of macrophages play a role in inhibiting the viral replication and eliminating the virus in vivo. It has been demonstrated that the proficiency of MCMV replication in the macrophages themselves determines the virulence and the virus-induced pathogenesis in vivo (6,45,46). The efficiency of inhibiting viral replication in macrophages themselves has been defined as the intrinsic antiviral activity of these cells (45).…”

“…In innate immunity to MCMV infection, NK cells (3,4), macrophages (5,6), and cytokines collaboratively act as the first line of antivirus defense. In contrast, the specific immune responses by CD4 ϩ and CD8 ϩ T cells help remove the virus late in infection, thus resulting in a protective effect from the virus-associated pathogenicities (7,8).…”

Host and Donor Immune Responses Contribute to Antiviral Effects of Amotosalen-Treated Donor Lymphocytes following Early Posttransplant Cytomegalovirus Infection

“…It has structural and biological similarities to human CMV (8,9), which causes similar disease in immunodeficient humans (10). First-line antiviral innate immunity against MCMV infection is mediated by the NK cells (11) and macrophages (12) and also by the CD4 Ϫ CD8 Ϫ (double negative (DN)) TCR␣␤ ϩ CD3 ϩ T cells (13). The second line of antiviral immunity requires adaptive immune responses with the expansion of Ag-specific T cells that eventually clear viral infected cells from the host tissues.…”

Cell-type specific activities of cytomegalovirus GPCR homologues

“…MCMV serves as good model for HCMV infection, because both viruses share many aspects of their pathogeneses and gene functionality, including several immune evasion mechanisms, such as inhibition of MHC-I presentation, chemokine and chemokine receptor homologs and evasion of NK cell recognition (Jackson et al, 2011b;Rawlinson et al, 1996;Scalzo et al, 2006). Although the murine model replicates acute, latent and chronic infection, it only partially emulates congenital infection due to its lack of or low transplacental transmission (Hamano et al, 1998;Tsutsui, 1995). Alternative methods have been developed to study congenital infection using the mouse model (both central nervous system and sensorineural hearing loss disorders), achieving comparable results by infecting directly the foetus or the placenta or by inoculating the newborn (Baskar et al, 1983;Bradford et al, 2015;Cekinovic et al, 2014;Ikuta et al, 2015;Juanjuan et al, 2011).…”