JPediatr(RioJ).2015;91(1):4---5
www.jped.com.br
EDITORIAL
Protective
effects
of
human
milk
antimicrobial
peptides
against
bacterial
infection
夽
,
夽夽
Efeitos
de
protec
¸ão
dos
peptídeos
antimicrobianos
do
leite
humano
contra
infecc
¸ões
bacterianas
Anders
P.
Hakansson
a,baDepartmentofMicrobiologyandImmunology,UniversityatBuffalo,StateUniversityofNewYork,Buffalo,UnitedStates bTheWitebskyCenterforMicrobialPathogenesisandImmunology,UniversityatBuffalo,StateUniversityofNewYork,Buffalo, UnitedStates
Breast-feedingprovidesthenursinginfantwithaplethora of molecules evolved to optimally develop the infant’s tissuesand organs.Human milkcontains numerous bioac-tive molecules that modulate the immune system as well as molecules with direct and indirect antimicrobial activitiesthat avoid overgrowth of potentially pathogenic microorganisms.Thecombinationofimmunmodulatoryand antimicrobial factors help the child to avoid the devel-opmentofinflammatory diseasesand childhoodinfection. Accordingly, thefeeding of formulaand other substitutes toinfantsisclearlycorrelatedwithanincreasedfrequency ofinflammatorydiseasessuchasallergies,colitis,juvenile diabetes,andchildhoodcancer,aswellasanincreased fre-quencyofinfections.Althoughsomeofthemechanismsand moleculesinvolvedinhumanmilk’sprotectionagainst infec-tionhave been well studied, thecomplete pictureof the verycomplexbiologyofthehumanmilkanti-microbial pro-tectionisnotyetclear.
DOIoforiginalarticle:
http://dx.doi.org/10.1016/j.jped.2014.05.006
夽 Pleasecitethisarticleas:HakanssonAP.Protectiveeffectsof
humanmilkantimicrobial peptides againstbacterial infection. J
Pediatr(RioJ).2015;91:4---5.
夽夽
SeepaperbyBaricellietal.inpages36---43.
E-mail:[email protected]
InastudypublishedinthisissueofJornaldePediatria,1 agroupfromInstitutoVenezolanodeInvestigaciones Cien-tíficas (IVIC), Caracas, Venezuela, ledby Dr. LuzThomas, presents evidence for the potential role of human beta-defensin-2 (hBD-2) from human milk in anti-microbial protectionagainstentericinfections andpotentiallyother infections as well. The authors measured the concentra-tion of hBD-2 in 100 human milk samples, 61 of which werefromcolostrumandtheremainingfrommaturemilk. Similar to what has been observed in one earlier study,2 colostrum samples contained significantly higher concen-trationsofhBD-2 thanmature milksamples;however,the concentrationsobservedherewereconsiderablyhigherthan the previously described, suggesting a possible contribu-tionofmilk-deriveddefensinstotheantimicrobialdefense of milk in vivo. The authors then produced recombinant hBD-2 and tested it against a broad range of poten-tially pathogenic enteric organisms, including Salmonella spp. and Escherichia coli strains, as well as strains of
Serratiamarcescens,Pseudomonasaeruginosa,and Acine-tobacter baumanii, and observed a sensitivity of these organismstohBD-2;theconcentrationsfoundinhumanmilk are likely to have an effect on these organisms in vivo. The results represent the first report of defensin-levels in milk from Latin American women and suggest a role for hBD-2 in the defense against enteric infections in infants.Thisinformationwillhopefullyspuronfuture stud-ies on milk antimicrobial peptides (AMPs) from this and
http://dx.doi.org/10.1016/j.jped.2014.10.001
Protectiveeffectsofhumanmilkantimicrobialpeptidesagainstbacterialinfection 5
other groups, increasingthe understanding of the roleof AMPs inboth immunemodulation andantimicrobial activ-ity.
To put this work in perspective, there is strong epidemiologic data suggesting a detrimental association betweenformula-feedingandinfectionininfants.3---5When comparing formula-fed and breast-fed infants, breast-fed infants present lower incidences of gastrointestinal, respiratory, urinary tract, and other infections, as well as lower child mortality.6 The main molecules associ-ated with this protection are antimicrobial factors in human milk that act either indirectly to block adher-ence of bacteria to mucosal surfaces or to neutralize bacteria, such as oligosaccharides, glycoconjugates, and immunoglobulins, or directly killing microbes, such as lactoferrin, lysozyme, peroxidases,fatty acids, and other molecules.7 Protection is further ameliorated by provid-ingfactorsthatmodulate theimmunesystem,5,8,9 suchas cytokinesand growth factors.Additionally, recent studies have shown that human milk contains its own micro-biome that, when provided to the infant, help establish a healthy microflora in the infant gut and other tissues, which also helpsto optimallydevelop the infantimmune system and to protect against overgrowth of pathogenic bacteria.10,11
TheroleofmilkasasourceofAMPsandtheroleofmilk AMPsintheprotectionagainstinfectionhasnotbeen inves-tigatedindepth.Initialstudiesinvestigatingtheexpression of defensins in mammary epithelium found expression of hBD-1,butnoexpressionofhBD-2wasobserved.12 Infact, the major beta-defensin produced in milk appears to be hBD-1.2,13 Yet,Armogidaetal.identifiedexpressionofthe
hbd-2 gene in 15% of the mammary epithelial cells they investigated,14andWangetal.wasrecentlythefirstgroup toshowsecretionofhBD-2inmilk.2
AMPs aremultifunctional defense molecules.15 Besides theiranti-microbialactivity,theyalsomodulatetheimmune systembyactivatingimmunecellsagainstpathogenic orga-nisms. Theirimportancein the defense againstinfections of mucosalliningssuchastheskin, respiratory tract,and gut, has been clearlydemonstrated using animal models, where thegenes formousedefensinsor cathelicidinhave been removedor theirexpressionhasbeen reduced.Such studieshaveshowntheimportanceofAMPsagainstvarious infectionsincludingthosecausedbyE.coliO157:H7, Strep-tococcuspyogenes,andStreptococcuspneumoniae,16---18and defensins and defensin-like molecules are known to con-tribute to bacterial clearance in the gut and lung.19 To conclude, the informationprovided by Baricelli et al.1 in the current issue of this journal should stimulate future studies in the field for several reasons. Firstly, further studieswillincreaseourunderstandingofthecomplex biol-ogy of human milk and its anti-microbial role in the gut and other mucosal tissues; secondly, the study of APMs, including defensins, are becoming more and more inter-esting as potential antibiotics in the era of antibiotic resistance.20
Conflicts
of
interest
Theauthordeclaresnoconflictsofinterest.
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