Breast milk induces the differentiation of monocytes into macrophages, promoting human cytomegalovirus infection.

Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus found in human breast milk that is frequently transmitted from HCMV-seropositive mothers to their infants during the postnatal period. Despite extensive research, the mechanisms underlying HCMV transmission from breast milk and the anatomical location at which virus transfer takes place remain unclear. Breast milk contains many uniquely differentiated macrophages that undergo specific morphological and functional modifications in the mammary gland during lactation. Although the existence of permissive HCMV infection in differentiated macrophages has been well-described, the role of breast milk in this process remains unknown. Herein, we report that exposure of isolated peripheral blood monocytes to breast milk induces their differentiation into macrophages that exhibit an M2 phenotype (CD14highCD163highCD68highCD206high) and promotes a productive and sustained HCMV infection. We also found that breast milk triggers macrophage proliferation and thus sustains a unique population of proliferating, long-lived, and HCMV-susceptible macrophages that are capable of ongoing production of infectious virions. These results suggest a mechanism that explains chronic HCMV shedding into the breast milk of postpartum seropositive mothers. We also found that HCMV virions released from breast milk-induced macrophages generate a productive infection in primary infant tonsil epithelial cells. Collectively, our results suggest that breast milk may facilitate HCMV transmission from mother to infant via the oropharyngeal mucosa. IMPORTANCE: While human cytomegalovirus (HCMV) is frequently detected in the breast milk of HCMV-seropositive women and is often transmitted to infants via breastfeeding, the mechanisms by which this transmission occurs remain unclear. In this study, we modeled HCMV transmission at the oropharyngeal mucosa. We treated human monocytes with breast milk to mimic the lactating mammary gland microenvironment. We found that monocytes differentiated into macrophages with an M2 phenotype, which were highly permissive for HCMV. We also discovered that breast milk induces macrophage proliferation. Thus, exposure to breast milk increased the number of HCMV-susceptible macrophages and supported high levels of infectious HCMV. We found that HCMV virions released from breast milk-induced macrophages could infect primary infant tonsil epithelial cells. Collectively, these findings reveal the dual role of breast milk that induces the differentiation and proliferation of macrophages in the mammary gland and thus facilitates mother-to-child HCMV transmission at the oropharyngeal mucosa.

A Holistic and Community-Based Service Program Promoting Mental Health among Latina Breast Cancer Survivors and Informal Caregivers.

This report discusses the components and uptake of a holistic-health community-based service program designed to promote mental health among Latina breast cancer survivors and their caregivers. Salud Holística para la Mujer's (SAHOM) strategic plan tackled all phases of the mental health prevention continuum and of the cancer care continuum.

HIV-1 Proteins gp120 and Tat Promote Epithelial-Mesenchymal Transition and Invasiveness of HPV-Positive and HPV-Negative Neoplastic Genital and Oral Epithelial Cells.

The incidence of human papillomavirus (HPV)-associated anogenital and oropharyngeal cancer in human immunodeficiency virus (HIV)-infected individuals is substantially higher than in HIV-uninfected individuals. HIV may also be a risk factor for the development of HPV-negative head and neck, liver, lung, and kidney cancer. However, the molecular mechanisms underlying HIV-1-associated increase of epithelial malignancies are not fully understood. Here, we showed that HPV-16-immortalized anal AKC-2 and cervical CaSki epithelial cells that undergo prolonged exposure to cell-free HIV-1 virions or HIV-1 viral proteins gp120 and tat respond with the epithelial-mesenchymal transition (EMT) and increased invasiveness. Similar responses were observed in HPV-16-infected SCC-47 and HPV-16-negative HSC-3 oral epithelial cancer cells that were cultured with these viral proteins. EMT induced by gp120 and tat led to detachment of poorly adherent cells from the culture substratum; these cells remained capable of reattachment, upon which they coexpressed both E-cadherin and vimentin, indicative of an intermediate stage of EMT. The reattached cells also expressed stem cell markers CD133 and CD44, which may play a critical role in cancer cell invasion and metastasis. Inhibition of transforming growth factor (TGF)-ß1 and MAPK signaling and vimentin expression, and restoration of E-cadherin expression reduced HIV-induced EMT and the invasive activity of HPV-16-immortalized anal and cervical epithelial cells. Collectively, our results suggest that these approaches along with HIV viral suppression with antiretroviral therapy (ART) might be useful to limit the role of HIV-1 infection in the acceleration of HPV-associated or HPV-independent epithelial neoplasia. IMPORTANCE HPV-16-immortalized genital and oral epithelial cells and HPV-negative oral cancer cells that undergo prolonged contact with cell-free HIV-1 virions or with viral proteins gp120 and tat respond by becoming more invasive. EMT cells induced by HIV-1 in cultures of HPV-16-immortalized anal and cervical epithelial cells express the stem cell markers CD133 and CD44. These results suggest that the interaction of HIV-1 with neoplastic epithelial cells may lead to their de-differentiation into cancer stem cells that are resistant to apoptosis and anti-cancer drugs. Thus, this pathway may play a critical role in the development of invasive cancer. Inhibition of TGF-ß1 and MAPK signaling and vimentin expression, and restoration of E-cadherin expression reduced HIV-induced EMT and the invasiveness of HPV-16-immortalized anal and cervical epithelial cells. Taken together, these results suggest that these approaches might be exploited to limit the role of HIV-1 infection in the acceleration of HPV-associated or HPV-independent epithelial neoplasia.