14 research outputs found
Innate immunity regulates adaptive immune response: lessons learned from studying the interplay between NK and CD8+ T cells during MCMV infection
Natural killer (NK) cells play a crucial role in early immune response against cytomegalovirus infection. A large and mounting body of data indicate that these cells are involved in the regulation of the adaptive immune response as well. By using mouse cytomegalovirus (MCMV) as a model, several groups provided novel insights into the role of NK cells in the development and kinetics of antiviral CD8+ T cell response. Depending on infection conditions, virus strain and the genetic background of mice used, NK cells are either positive or negative regulators of the CD8+ T cell response. At present, there is no unique explanation for the observed differences between various experimental systems used. In this review we discuss the mechanisms involved in the interplay between NK and CD8+ T cells in the early control of MCMV infection
The m15 Locus of Murine Cytomegalovirus Modulates Natural Killer Cell Responses to Promote Dissemination to the Salivary Glands and Viral Shedding
As the largest herpesviruses, the 230 kb genomes of cytomegaloviruses (CMVs) have increased our understanding of host immunity and viral escape mechanisms, although many of the annotated genes remain as yet uncharacterised. Here we identify the m15 locus of murine CMV (MCMV) as a viral modulator of natural killer (NK) cell immunity. We show that, rather than discrete transcripts from the m14, m15 and m16 genes as annotated, there are five 3ā²-coterminal transcripts expressed over this region, all utilising a consensus polyA tail at the end of the m16 gene. Functional inactivation of any one of these genes had no measurable impact on viral replication. However, disruption of all five transcripts led to significantly attenuated dissemination to, and replication in, the salivary glands of multiple strains of mice, but normal growth during acute infection. Disruption of the m15 locus was associated with heightened NK cell responses, including enhanced proliferation and IFNĪ³ production. Depletion of NK cells, but not T cells, rescued salivary gland replication and viral shedding. These data demonstrate the identification of multiple transcripts expressed by a single locus which modulate, perhaps in a concerted fashion, the function of anti-viral NK cells
Braināresident memory CD8+ T cells induced by congenital CMV infection prevent brain pathology and virus reactivation
Congenital HCMV infection is a leading infectious cause of longāterm neurodevelopmental sequelae. Infection of newborn mice with mouse cytomegalovirus (MCMV) intraperitoneally is a wellāestablished model of congenital human cytomegalovirus infection, which best recapitulates the hematogenous route of virus spread to brain and subsequent pathology. Here, we used this model to investigate the role, dynamics, and phenotype of CD8+ T cells in the brain following infection of newborn mice. We show that CD8+ T cells infiltrate the brain and form a pool of tissueāresident memory T cells (TRM cells) that persist for lifetime. Adoptively transferred virusāspecific CD8+ T cells provide protection against primary MCMV infection in newborn mice, reduce brain pathology, and remain in the brain as TRM cells. Brain CD8+ TRM cells were longā lived, slowly proliferating cells able to respond to local challenge infection. Importantly, brain CD8+ TRM cells controlled latent MCMV and their depletion resulted in virus reactivation and enhanced inflammation in brain
Short history of just mentorship and support
Since its foundation in 1992, the Croatian Medical Journal (CMJ)
has followed the strict standards of quality in the scientific publishing.
However, the Journal has been aware that its specific position
demands more than just following the already established rules.
From the very beginning, the Journal declared an āauthor-helpful
policy,ā stating that ājournal editors should have a major role in
training authors in science communication, especially in smaller and
developing scientific communities. Journal authors usually send scientifically
acceptable but poorly prepared articles and it is a pity to
lose valid data because of their poor presentation.ā (1,2).
In brief, the editors and editorial staff of the CMJ have been well
aware that the skills of scientific reporting and publishing in our academic
community are not developed and that valuable research results
and valid data are being lost because of poor presentation. To
be perfectly honest, ten years ago this statement looked like a nice
promise, one of the many we in academic medicine learnt not to take
too seriously