Purchase this article with an account.
Ujjaldeep Jaggi, Harry Matundan, Jack Yu, Homayon Ghiasi; Effect of further shifting the M2-like macrophage responses by cellular adjuvant on primary and latent HSV-1 infection. Invest. Ophthalmol. Vis. Sci. 2021;62(8):1966.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Macrophages are one of the dominant infiltrates in the corneas of ocularly infected mice. Previously, we demonstrated that M2 macrophages have a protective effect on ocular virus, eye disease, latency, and reactivation than M1 macrophages using HSV-1 infected WT mice. To further explore the role of M1 and M2 macrophages on the HSV-1 responses, we used M2-/- (GATA3 deleted) and M2-OE (GATA3 overexpressed) mice and infected them with HSV-IL4 (to further push toward M2) or HSV-IFNg (to further push toward M1).
M2-/- and M2-OE mice were ocularly infected with 2X105 pfu/eye of HSV-1 recombinant viruses expressing IL4 or IFNg or parental control virus. Following ocular infection with each virus, primary virus replication in the eye, viral and cellular expressions in the cornea and trigeminal ganglia (TG) on various times post-infection (PI) and survival, corneal scarring (CS) and latency-reactivation on day 28 PI were determined.
Primary infection in the eye was significantly reduced in HSV-IL4 infected mice on day 3 PI compared to mice infected with either HSV-IFNg or control viruses. CS was higher in HSV-IFNg infected mice compared with HSV-IL4 or control viruses. Latent infection in TG was reduced in both HSV-IL4 and HSV-IFNg groups compared with the parental virus, while the level of latency in HSV-IL4 infected mice was significantly lower than HSV-IFNg infected mice. In addition, reactivation was also lower in HSV-IL4 infected mice as compared with HSV-IFNg and control infected mice.
Our findings demonstrate that: 1) Both HSV-IL4 and HSV-IFNg viruses shifted macrophage polarization toward M2 and M1, respectively; and 2) HSV-IL4 was more effective in providing protection against both primary and latent infection and reactivation compared to HSV-IFNg or parental virus. Our results suggest that inclusion of cellular factor(s) as part of a vaccination regiment to coax responses of macrophages toward M2 polarization, as compared to the M1 polarization, may further improve vaccine efficacy against ocular HSV-1 replication and latency-reactivation in the ocularly infected mice.
This is a 2021 ARVO Annual Meeting abstract.
This PDF is available to Subscribers Only