The Prevalence of High Carcinogenic Risk of HPV Genotypes among HIV-Positive and HIV-Negative MSM from Russia.

OBJECTIVE: Men who have sex with men (MSM) have a high risk of lifelong anal cancer caused by high-risk human papillomavirus (HR HPV) infections. The aim of this study was to investigate the prevalence of anal canal HR HPV infection among men who have sex with men (MSM) with and without HIV infection in Moscow (Russia). We evaluated associations of some HIV coinfections (HSV and CMV) and HPV distribution among MSM with and without HIV infection. METHODS: Two groups of HIV-positive (n = 60) and HIV-negative (n = 60) MSM were evaluated in the study. Fourteen high-risk (HR) HPV types, HSV1/2, and CMV were investigated in men anal swabs. RESULTS: HR HPVs were found with nearly the same frequency of 66.7% in both groups: HIV-positive and HIV-negative MSM. HIV-positive status was statistically associated with the presence of several (more than two) HPV types (p=0.044). The most prevalent HR HPV genotypes were HPV18, HPV16, HPV56, and HPV33 for HIV-positive MSM and HPV56, HPV51, HPV66, and HPV16 for HIV-negatives. We found a statistically significant association of five HR HPV types with HIV status of MSM: HPV16 (p=0.028), HPV18 (p=0.00006), HPV58 (p=0.003), HPV33 (p=0.019), and HPV39 (p=0.026). The frequency of HSV1 (1.7%) and HSV2 (10%) infections and CMV (3.3%) infection was evaluated in the group of HIV-positive MSM. The frequency of HSV1 (5%) and HSV2 (6.7%) infections and CMV (0%) infection was evaluated, as well, in the group of HIV-negative MSM. CONCLUSION: Multiple HPV genotypes were detected significantly more often than single HPV genotype in the group of HIV-positive MSM. According to our data, 25% of HIV-positive MSM have HPV39; this is the only one of the five types of HR HPV (16, 18, 58, 33, and 39) associated with this group of MSM that has not yet been included in the HPV vaccines available on the market.

Activated Macrophages of Monocytic Origin Predominantly Express Proinflammatory Cytokine Genes, Whereas Kupffer Cells Predominantly Express Anti-Inflammatory Cytokine Genes.

In the central nervous system and in the liver, the macrophage populations are represented exclusively by descendants of the hematopoietic progenitor cells of the yolk sac. The reasons for such differential distribution of macrophages are not fully understood. We found that, as can be judged by corresponding changes in the expression of CD86 and CD163 markers, the transient macrophages of monocytic lineage are more sensitive to activating stimuli. The two macrophage populations have distinct patterns of gene expression, which is particularly noticeable for M1- and M2-associated genes. For instance, Kupffer cells more readily develop and longer maintain the elevated expression levels of Il4, Il10, and Il13 upon the activation; by contrast, the macrophages of monocytic lineage express Il1b, Il12a, and Tnfα upon the activation. The obtained results allow us to conclude that the in vitro activated Kupffer cells of the liver are committed to M2 phenotype, whereas the in vitro activated monocyte-derived macrophages show a typical M1 behavior. These observations are likely to reflect the situation in the in vivo microenvironments.

Dynamics of macrophage populations of the liver after subtotal hepatectomy in rats.

BACKGROUND: In many clinical cases of extensive liver resection (e.g. due to malignancy), the residual portion is too small to maintain the body homeostasis. The resulting acute liver failure is associated with the compensatory growth inhibition, which is a typical manifestation of the 'small for size' liver syndrome. The study investigates possible causes of the delayed onset of hepatocyte proliferation after subtotal hepatectomy (80% liver resection) in rats. RESULTS: The data indicate that the growth inhibition correlates with delayed upregulation of the Tnf gene expression and low content of the corresponding Tnfα protein within the residual hepatic tissue. Considering the involvement of Tnf/Tnfα, the observed growth inhibition may be related to particular properties of liver macrophages - the resident Kupffer cells with CD68+CX1CR3-CD11b- phenotype. CONCLUSIONS: The delayed onset of hepatocyte proliferation correlates with low levels of Tnfα in the residual hepatic tissue. The observed growth inhibition possibly reflects specific composition of macrophage population of the liver. It is entirely composed of embryonically-derived Kupffer cells, which express the 'proregeneratory' M2 macrophage-specific marker CD206 in the course of regeneration.

Multipotent stromal cells stimulate liver regeneration by influencing the macrophage polarization in rat.

AIM: To investigate the influence of the umbilical cord-derived multipotent stromal cells (MSCs) on recovery of the liver after the subtotal resection, that is, removal of 80% of the organ mass, a renowned model of the small-for-size liver remnant syndrome. METHODS: The MSCs were obtained from the intervascular tissue of umbilical cords, dissected from rat fetuses, by the explant culture technique. The vital labeling of MSCs with РКН26 was carried out on the 3rd passage. The subtotal resection was performed on male Sprague-Dawley rats. The experimental group animals received a transplant 106 MSCs infused into the spleen. Hepatocyte proliferation was assessed by counting of either mitotic figures or Ki67-positive cells in microscopic images. MSC differentiation was assessed with antibodies to hepatocyte-specific marker cytokeratin 18 (CK18), cholangiocyte-specific protein CK19, smooth muscle cell-specific protein α-SMA, the endothelial cell marker CD31, or the active fibroblast marker FAPα. Total macrophages of the liver were selectively stained in cryosections incubated with anti-CD68 antibodies (1:100, Abcam), while the M2a and M2c macrophage populations were selectively stained with anti-CD206 antibodies. Expression of interleukin and growth factor genes was evaluated with PCR-RT. RESULTS: Intrasplenic allogeneic transplantation of the umbilical cord-derived multipotent stromal cells stimulates reparative processes within the residual liver tissue after subtotal resection (removal of 80% of the organ mass), as indicated by increased rates of hepatocyte proliferation and accelerated organ mass recovery. These effects may result from paracrine influence of the transplanted cells on the resident macrophage population of the liver. The transplantation favors polarization of macrophages to M2 phenotype (the M2-polarized macrophages specifically express CD206; they are known to suppress inflammation and support tissue repair). No differentiation of the transplanted cells into any of the liver cell types have been observed in the study. CONCLUSION: We found no direct evidence for the paracrine effect of MSCs on liver regeneration after the subtotal liver resection in rats. However, the paracrine mechanism of the therapeutic activity of transplanted MSC is indirectly indicated by a decrease in the total number of CD68 + macrophages and an increase in the proportion of M2 pro-repair macrophages in the regenerating liver as compared to animals in which the transplantation was only mimicked.