All Posts Tagged With: "peripheral blood mononuclear cells"

Immune Function in Early Lyme Infection

Link: http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1001144

Excerpt:

If insufficiently treated, Lyme borreliosis can evolve into an
inflammatory disorder affecting skin, joints, and the CNS. Early
innate immunity may determine host responses targeting infection.
Thus, we sought to characterize the immediate cytokine storm
associated with exposure of PBMC to moderate levels of live
Borrelia burgdorferi. Since
Th17 cytokines are connected to host defense against
extracellular bacteria, we focused on interleukin (IL)-17 and
IL-22. Here, we report that, despite induction of inflammatory
cytokines including IL-23, IL-17 remained barely detectable in
response to B. burgdorferi. In contrast, T cell-dependent
expression of IL-22 became evident within 10 h of exposure to the
spirochetes. This dichotomy was unrelated to interferon-? but to
a large part dependent on caspase-1 and IL-1 bioactivity derived
from monocytes. In fact, IL-1? as a single stimulus induced IL-22
but not IL-17. Neutrophils display antibacterial activity against
B. burgdorferi, particularly when opsonized by antibodies. Since
neutrophilic inflammation, indicative of IL-17 bioactivity, is
scarcely observed in Erythema migrans, a manifestation of skin
inflammation after infection, protective and antibacterial
properties of IL-22 may close this gap and serve essential
functions in the initial phase of spirochete infection.

Susceptibility of xenotropic murine leukemia to XMRV

Linda’s comments:  There is a lot of controversy regarding XMRV and doctors are scrambling to find some answers.  Doctors are now thinking that this virus is in Lyme patients. 

Excerpt:

Xenotropic murine leukemia virus-related virus (XMRV) is a recently discovered gammaretrovirus that has been linked to prostate cancer and chronic fatigue syndrome. This virus is therefore an important potential human pathogen and, as such, it is essential to understand its host cell tropism. Intriguingly, infectious virus has been recovered from patient-derived peripheral blood mononuclear cells. These cells express several antiviral restriction factors that are capable of inhibiting the replication of a wide range of retroviruses, including other gamma retroviruses. This raises the possibility that, similar to HIV, XMRV may have acquired resistance to restriction. We therefore investigated the susceptibility of XMRV to a panel of different restriction factors. We found that both human APOBEC3 and tetherin proteins are able to block XMRV replication. Expression of human TRIM5alpha, however, had no effect on viral infectivity. There was no evidence that XMRV expressed countermeasures to overcome restriction. In addition, the virus was inhibited by factors from nonhuman species, including mouse Apobec3, tetherin, and Fv1 proteins. These results have important implications for predicting the natural target cells for XMRV replication, for relating infection to viral pathogenicity and pathology, and for the design of model systems with which to study XMRV-related diseases.