Added: Arline Heitmann - Date: 19.11.2021 17:08 - Views: 29094 - Clicks: 9042
Paradoxically, exclusive breastfeeding regardless of the HIV status of the mother has led to a ificant 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 ificance 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. 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, lactating hookers the elderly. Although it had been recognized for centuries that breastfeeding and infant health lactating hookers associated, one of the earliest systematic studies to demonstrate this was conducted by Grulee et al.
They studied over 20, mother—infant dy and showed that compared with breastfed infants, non-breastfed infants had 3. These differences clearly indicate that breastfeeding and breast milk have protective activities. Indeed, it has been established that human milk contains a growing list of bioactive molecules, including components of the innate and adaptive immune system of the mother, primarily secretory immunoglobulin A SIgA 2 — 4. The title of this review is taken, in part, from Dr.
David S. Newborns and infants bear the greatest burden of infectious disease. The World Health Organization estimates Universal breastfeeding could prevent annual deaths ofchildren under the age of 5 years as well as 20, breast cancer deaths each year 7. Economic losses close to three billion dollars per year are associated with not breastfeeding 8.
Breastfeeding unquestionably protects against death and disease. Non-breastfed infants younger than 6 months had 3. These protective effects of breast milk undoubtedly can be attributed to the multitude of bioactive molecules that have been shown protective against infections, reducing inflammation, facilitating immune system and organ development, and beneficially influencing the infant microbiome. Lactating hookers the majority of bioactive factors in milk have not yet been identified, characterization of novel factors in milk will open the door for the development of novel antimicrobial immunotherapeutics.
The benefits of breastfeeding for infants arise from the lactating hookers composition of breast milk.
Breast milk completely nourishes the infant while establishing and promoting a healthy microbiome, and providing passive protection through maternal innate and adaptive immunological factors. Breastfeeding is well recognized to protect infants against gastrointestinal and respiratory infections, diarrheal diseases, and provides long-term health benefits 13 — Additional socioeconomic benefits extend to the mother and family since breastfeeding promotes child spacing, social acceptance of the nursing woman, lactating hookers is cost effective 17 It became clear in the s that breast milk serves as a medium for HIV-1 transmission.
In addition to postnatal transmission via breast milk, infants can become infected from their HIV-infected mothers in utero or following exposure to maternal fluids during parturition However, this risk is ificantly attenuated if the mother is given antiretroviral ARV therapy pre- and post-cesarean delivery The past decade has shown ificant progress in the prevention of mother-to-child transmission PMTCT of HIV globally through improved access to ARV therapies for women and infants, as well as the universal promotion of exclusive breastfeeding EBF when safe and sustainable alternatives are not readily available.
As a result of these prevention strategies, for the first time the elimination of MTCT of HIV is considered a realistic public health goal For example, ARV therapies such as single-dose nevirapine, given to the mother during delivery and the infant within 72 h postpartum has proven effective and has undoubtedly played an important role in the drastic decrease of approximatelycases of MTCT of HIV in tocases in However, follow-up studies revealed that the HIV infection reappeared.
In many resource-limited areas where HIV-infected mothers have inadequate access to ARV therapies, mothers are encouraged to exclusively breastfeed their infants as an alternative preventive intervention Thus, EBF infants of HIV-positive mothers who regularly consume HIV containing breast milk have increased protection against infection compared with mixed fed infants who are less frequently exposed to the virus. Kuhn et al. While the reasons underlying this phenomenon remain unanswered, they have been closely linked with innate immune factors in breast milk 31 We have hypothesized that short-lived innate factors in milk would have to be consistently provided to the nursing infant via EBF to sustain a protective innate immune threshold to prevent HIV transmission via milk.
Although a of comprehensive reviews of breastfeeding and HIV transmission have been published 3435this article will highlight some lactating hookers the current insights into biological and immunological factors in breast milk that are associated with protection from HIV infection via breastfeeding. Humans are mammals because we have mammary glands which many believe evolved as part of the innate immune system Innate and adaptive immune factors in breast milk have been shown to play critical evolutionary roles in protecting newborn infants against a wide variety of infections.
Recently, of about proteins identified in a pooled milk sample, were novel Consequently, identification of these novel factors in milk and elucidation of their functions could inform the development of novel therapeutics or vaccines. Non-cellular factors in breast milk that have been attributed to the protection from HIV infection observed in breastfed infants include innate factors, cytokines, and oligosaccharides 313238 Table 1. For other factors such as HIV-specific antibodies, the data are less clear 39 Specifically, lactoferrin, whose levels have been shown to correlate with reduced MTCT of HIV 45has been shown in vitro to bind to the V3 loop of gp, thus inhibiting gp interaction with host CD4 receptor Lactoferrin has also been shown to inhibit bacterial-induced inflammation 47 Similarly, SLPI levels correlated with decreased MTCT HIV transmission through breast milk 49which is supported by in vitro studies indicating that it interacts with target cells to inhibit viral entry Figure 1.
Schematic representation of the protective components in breast milk. In addition, the foreign antigens likely increase inflammation and recruit increased target cells leading to increased HIV transmission. Another recently identified innate factor in breast milk is Tenascin-C TNCwhich has the capability to neutralize HIV-1 virions by binding to the chemokine co-receptor binding site on the HIV-1 envelope TNC is also an extracellular matrix protein ly shown to be involved in wound healing and fetal brain development 52 Unfortunately, it was recently shown that the amount of TNC correlated only weakly with overall innate HIV-neutralizing activity of breast milk of uninfected women, indicating that the amount of TNC in mucosal fluids was inadequate to impede HIV transmission We were the first to demonstrate that breast milk sTLR2 directly interacts with specific HIV-1 structural proteins, namely, p17, p24, and gp41, thus inhibiting cellular activation and cell-free HIV infection in vitro 44 Furthermore, sTLR2 has known antimicrobial properties that ificantly inhibit pro-inflammatory cytokine production in human intestinal epithelial cells IECsas well as reducing lactating hookers inflammation in mice without impairing microbial clearance 445556and therefore, if developed, may provide a novel prophylactic anti-inflammatory agent in breastfeeding lactating hookers Our lab went on to demonstrate that elafin is times more potent against HIV compared with its precursor, trappin-2, and part of the antiviral activity of this antiprotease was due to modulation of innate sensing 59 — Further, these factors function concomitantly to control aberrant microbial-induced inflammation, have direct antimicrobial effects, as was most recently shown by Pfaender et al.
Breast milk contains a range of cytokines, some of which could potentially influence immune function and directly correlate with MTCT HIV transmission. In sub-Saharan Africa, HEU infants suffer up to four times increased risk of dying in the first 2 years of life and increased risk for infectious morbidity A of studies have been conducted on HEU infants relating breastfeeding to their health.
One particular study conducted by John-Stewart et al. It can be concluded from these studies that breastfeeding HEU infants has many benefits including lower risk of HIV infection, pneumonia, and infectious diseases. In another study, Bork 68 discovered that HEU infants in Kesho Bora who were not breastfed had an increased risk of infection between birth and 2.
In total, infants were investigated for 2 years to see the health implications particularly fever, diarrhea, vomiting, and other serious infections in relation to feeding method. More than different HMOs have been identified and are unique to human milk 69 — Together, HMOs make up the third largest component of breast milk and are completely indigestible to infants. Although once believed to have no biological ificance, it is now clear that they can function as pathogen blocking agents or decoy receptors for pathogenic microbes 72have direct aling ability 7374and play a major role in establishing a healthy microbiome 75 — To cause intestinal infection, bacterial and viral pathogens often adhere to lectin—glycan structures on mucosal surfaces to initiate colonization.
Although recently contested 79manuscripts have lactating hookers that HMOs directly reduce microbial infections by serving as soluble decoy receptors, which prevent pathogen binding to these glycans 80 The lactating hookers effects of this HMO on reducing C. In addition, HMOs have antiviral properties. Human milk oligosaccharides may also directly modulate IEC and immune cell responses.
Together, these data suggest HMOs may contribute to allergy prevention. HMOs, as a complex mixture of free glycans, provide a perfect growth advantage to Bifidobacterium infantis 97which has evolved to contain lactating hookers glycosyl hydrolases necessary to utilize HMOs internally 98 resulting in beneficial short-chain fatty acids and other metabolite production.
This favors the growth of commensals in addition to lowering luminal pH There are various different protective factors in milk. Defense factors include maternal-derived SIgA and SIgM, oligosaccharides, anti-inflammatory factors, antioxidants, epithelial growth factors, and the aforementioned leukocytes and cytokines One of the most prevalent antibodies present in breast milk, SIgA, is produced by plasma cells in the mammary gland In mucosal tissues, Lactating hookers is produced as a dimer in which two immunoglobulin monomers are linked by the J chain.
Upward of 75, IgA-producing plasma cells are present in the normal human lactating hookers with 3—4 g of IgA secreted daily. This ificantly exceeds the production of all other immunoglobulin classes. Continuous production of large amounts of SIgA occurs in the absence of pathogen invasion and is driven by recognition of resident microbiota.
IgA secreted in the gut lumen binds to mucus coating epithelial surfaces where it is involved in preventing attachment to the epithelium and invasion by pathogens. IgA can also neutralize microbial toxins, bacterial lipopolysaccharide, and viruses it encounters. Full-term neonates are deficient in SIgA especially at the colostral stage of lactation. Breastfeeding provides specific maternal-derived SIgA antibodies to protect the infant Similarly, SIgM is also transferred via breast milk and is key in combating neonatal enteric antigens such as microorganisms and food proteins Indeed, there are arguments that infected cells both facilitate and protect against HIV transmission in breastfeeding infants — Although most studies of cells in breast milk have focused on leukocytes and their immunological activities, particularly postpartum, more recent exciting studies have identified pluripotent stem cells in breast milk.
Using a well-known stem cell marker found in neural, bone marrow, pancreatic and epithelial stem cells, nestin —Cregan et al. Moreover, some investigators hypothesize that these cells may promote growth and development of the infant Indeed, in mouse models, ingested milk stem cells were shown to survive in the gastrointestinal tract Given these insightful studies, it is clear that additional investigation of hBSCs will not only further our understanding of how hBSCs ingestion in early life may reduce disease burden in later life but may also provide novel regenerative medicine to replenish and restore damaged tissues.
Importantly, it has been shown that multiple innate immune factors that are endogenous to breast milk, including mucin, SLPI, sTLR2, lactoferrin, lysozyme, and oligosaccharides can effectively inactivate CFV infection in vitro 313244555888—whereas innate immune factors seemingly have little to no effect on CAV infection in vitro 32 These observations suggest that CFV likely plays an important role in breast milk transmission.
Given these contradictory studies, it could be argued that multiple factors including overall maternal viral load, breast health i. Based on a collection of studies examining cell-free and cell-associated HIV-1, there is a clear trend suggesting that CFV is more predominantly associated with viral load in the later stages postpartum. Ndirangu et al. Up until 6 months, however, the viral load levels were analogous Similarly, Koulinska et al.
In the earlier stages postpartum in both of the aforementioned studies, a fold increase in both viral levels lactating hookers to a 3-fold increase in viral transmission 35 The first demonstration of selective transmission of HIV variants was conducted by Wolinsky et al. Similar to other mucosally transmitted founder viruses, postnatal acquisition is primarily CCR5 tropic Phylogenetic comparison of milk and plasma envelope gene sequences revealed that monotypic viruses are ificantly more common in milk as compared with plasma from the same mother, thus suggesting that the majority of breast milk viruses are produced by infected cells of the mammary gland.
In addition, infant and maternal HIV variants did not differ in their sensitivity to broadly neutralizing antibodies; however, the viruses from transmitting mothers tended to be less sensitive to antibody-dependent neutralization By contrast, other studies suggest that viral lactating hookers found in the breast milk and plasma of infected mothers were genetically similar It is important to note that although MECs can endocytose cell-free HIV ; whether or not the virus integrates into the host genome remains controversial Indeed, there are arguments that infected cells both facilitate and protect against HIV-1 transmission in breastfeeding infants,Lactating hookers
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