Mother-to-Child HIV-1 Transmission Events Are Differentially Impacted by Breast Milk and Its Components from HIV-1-Infected Women

Abstract

Breast milk is a vehicle of infection and source of protection in post-natal mother-to-child HIV-1 transmission (MTCT). Understanding the mechanism by which breast milk limits vertical transmission will provide critical insight into the design of preventive and therapeutic approaches to interrupt HIV-1 mucosal transmission. However, characterization of the inhibitory activity of breast milk in human intestinal mucosa, the portal of entry in postnatal MTCT, has been constrained by the limited availability of primary mucosal target cells and tissues to recapitulate mucosal transmission ex vivo. Here, we characterized the impact of skimmed breast milk, breast milk antibodies (Igs) and non-Ig components from HIV-1-infected Ugandan women on the major events of HIV-1 mucosal transmission using primary human intestinal cells and tissues. HIV-1-specific IgG antibodies and non-Ig components in breast milk inhibited the uptake of Ugandan HIV-1 isolates by primary human intestinal epithelial cells, viral replication in and transport of HIV-1- bearing dendritic cells through the human intestinal mucosa. Breast milk HIV-1-specific IgG and IgA, as well as innate factors, blocked the uptake and transport of HIV-1 through intestinal mucosa. Thus, breast milk components have distinct and complementary effects in reducing HIV-1 uptake, transport through and replication in the intestinal mucosa and, therefore, likely contribute to preventing postnatal HIV-1 transmission. Our data suggests that a successful preventive or therapeutic approach would require multiple immune factors acting at multiple steps in the HIV-1 mucosal transmission process.

A realist review of infant feeding counselling to increase exclusive breastfeeding by HIV-positive women in sub Saharan-Africa: what works for whom and in what contexts

“…Because of this, the most recent WHO guidelines on HIV and Infant Feeding promote exclusive breastfeeding, for the optimal balance between malnutrition prevention and reduction of vertical transmission risk for HIV in areas where resources are limited [10]. Whilst exclusive breastfeeding is promoted in the context of ART for mother and infant, it is still encouraged even in the unavailability of ART, as evidence shows the majority of infants exposed to HIV who are exclusively breastfed do not contract HIV [10, 11]. It is theorized that mixed feeding, defined as some breastfeeding with the addition of other nutrients, affects gastrointestinal mucosa integrity and potentially facilitates MTCT of HIV [1, 8].…”

Phagocytosis of a Model Human Immunodeficiency Virus Target by Human Breast Milk Leukocytes Is Predominantly Granulocyte-Driven When Elicited by Specific Antibody

“…1,2 Even in the absence of antiretroviral drugs, only *10-15% of infants breastfed by HIV-infected mothers become infected, suggesting a strong protective effect of BM. [1][2][3][4][5] Adherence to maternal highly active antiretroviral therapy (HAART) reduces MTCT to *1-5%, although there are concerns of toxicity and drug resistance, and the availability and adherence to HAART are not guaranteed. [6][7][8][9][10][11][12] As diarrheal and respiratory diseases are responsible for substantial rates of mortality among infants in resourcelimited countries, and these illnesses are significantly reduced by exclusive breastfeeding, the benefits to HIVinfected mothers of breastfeeding far outweigh the risks.…”

Baicalin Ameliorates Experimental Liver Cholestasis in Mice by Modulation of Oxidative Stress, Inflammation, and NRF2 Transcription Factor

“…The proposed mechanism of liver fibrosis includes oxidative tissue injury, mitochondrial dysregulation, and inflammation, which lead to apoptotic and necrotic cell death [ 5 , 6 ]. Liver fibrogenic cells (myofibroblasts), mainly derived from hepatic stellate cells (HSC), play a central role during liver fibrosis [ 7 ].…”