Breastfeeding Behaviors and the Innate Immune System of Human Milk: Working Together to Protect Infants against Inflammation, HIV-1, and Other Infections

Abstract

The majority of infants’ breastfeeding from their HIV-infected mothers do not acquire HIV-1 infection despite exposure to cell-free virus and cell-associated virus in HIV-infected breast milk. Paradoxically, exclusive breastfeeding regardless of the HIV status of the mother has led to a significant decrease in mother-to-child transmission (MTCT) compared with non-exclusive breastfeeding. Although it remains unclear how these HIV-exposed infants remain uninfected despite repeated and prolonged exposure to HIV-1, the low rate of transmission is suggestive of a multitude of protective, short-lived bioactive innate immune factors in breast milk. Indeed, recent studies of soluble factors in breast milk shed new light on mechanisms of neonatal HIV-1 protection. This review highlights the role and significance of innate immune factors in HIV-1 susceptibility and infection. Prevention of MTCT of HIV-1 is likely due to multiple factors, including innate immune factors such as lactoferrin and elafin among many others. In pursuing this field, our lab was the first to show that soluble toll-like receptor 2 (sTLR2) directly inhibits HIV infection, integration, and inflammation. More recently, we demonstrated that sTLR2 directly binds to selective HIV-1 proteins, including p17, gp41, and p24, leading to significantly reduced NFκB activation, interleukin-8 production, CCR5 expression, and HIV infection in a dose-dependent manner. Thus, a clearer understanding of soluble milk-derived innate factors with known antiviral functions may provide new therapeutic insights to reduce vertical HIV-1 transmission and will have important implications for protection against HIV-1 infection at other mucosal sites. Furthermore, innate bioactive factors identified in human milk may serve not only in protecting infants against infections and inflammation but also the elderly; thus, opening the door for novel innate immune therapeutics to protect newborns, infants, adults, and the elderly.

Human milk oligosaccharides promote immune tolerance via direct interactions with human dendritic cells

“…In the past decades, there has been a growing appreciation that breast milk beneficially supports the innate immune system and modulates microbiota composition during the first months of life. Breastfeeding is known to reduce the risk of inflammatory diseases , infectious diseases , asthma and allergic disease , as well as autoimmune diseases . Among the various bioactive components in breast milk, human milk oligosaccharides (HMOS) have been suggested to play a key role .…”

Leche Materna: Efectos de los oligosacáridos de la leche materna en el crecimiento y desarrollo de los lactantes (Parte 3)

“…Una publicación reciente discutió los mecanismos a través de los cuales la maduración del sistema inmune del feto se produce in útero sin desencadenar reacciones del tipo "el feto-versus-la madre" y de qué manera los HMOs favorecen este desarrollo postnatal 13 . Los HMOs fortalecerían la inmunidad innata, especialmente a nivel del tubo digestivo, previniendo reacciones inflamatorias intensas y descontroladas.…”

Leche Materna: Características funcionales de los oligosacáridos de la leche materna (Parte 2)

“…Algunos de estos agentes expresan en su cápside glucanos que les permiten unirse a las células intestinales del huésped. En los lactantes amamantados, la superficie del epitelio intestinal está cubierta por altas concentraciones de HMOs que pueden bloquear el acceso del virus de la inmunodeficiencia humana (VIH) a los enterocitos; por lo tanto, estos compuestos protegerían a los lactantes durante su exposición al virus presente en la leche de sus madres infectadas e inhibiría la transmisión vertical 26,48 .…”

“…Como parte de un estudio en que la transmisión del VIH fue investigada en madres infectadas 4 meses después de la suspensión de la lactancia, 167 madres portadoras del virus fueron contactadas para investigar los mecanismos de transmisión, su eficiencia y el papel de la leche materna y sus factores defensivos, incluyendo los HMOs 48 . Ochenta y una de ellas habían transmitido el virus a su hijo, 86 madres también infectadas no habían transmitido el virus y un grupo adicional de 36 madres no estaban infectadas (controles) 1,36 .…”