PROTECTIVE ROLE OF HUMAN LACTOFERRIN AGAINST INVASION OF Shigella flexneri M90T. ♦ 707

Gomez, Henry F.; Siddiqui, Mustafa M.; Diaz-Gonzalez, Vicente A.; Caceres, Enrique; Herrera, Irene; Pickering, Larry K.; Cleary, Thomas G.

doi:10.1203/00006450-199704001-00727

Cited by 10 publications

(13 citation statements)

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“…Previously identified compounds have been shown to inhibit T3SS function and pathogenesis. Lactoferrin inhibits T3SS-dependent invasion by Shigella by causing degradation of IpaA and IpaB (41,42). Other novel inhibitors of T3SS function have also been shown to inhibit bacterial virulence.…”

Section: Inhibitors Of T3sssmentioning

confidence: 99%

Type III Secretion Systems and Disease

2007

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SUMMARY Type III secretion systems (T3SSs) are complex bacterial structures that provide gram-negative pathogens with a unique virulence mechanism enabling them to inject bacterial effector proteins directly into the host cell cytoplasm, bypassing the extracellular milieu. Although the effector proteins vary among different T3SS pathogens, common pathogenic mechanisms emerge, including interference with the host cell cytoskeleton to promote attachment and invasion, interference with cellular trafficking processes, cytotoxicity and barrier dysfunction, and immune system subversion. The activity of the T3SSs correlates closely with infection progression and outcome, both in animal models and in human infection. Therefore, to facilitate patient care and improve outcomes, it is important to understand the T3SS-mediated virulence processes and to target T3SSs in therapeutic and prophylactic development efforts.

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Section: Inhibitors Of T3sssmentioning

confidence: 99%

Type III Secretion Systems and Disease

2007

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“…Clinical studies reported by Mårild et al (2004) also suggest that breast-feeding protects against urinary tract infections in children. Furthermore, some experimental studies (Edde et al 2001;Gomez et al 2001) suggest that lactoferrin may act against intestinal infections caused by E. coli and Shigella flexneri.…”

Section: Lactoferrinmentioning

confidence: 99%

Session 1: Feeding and infant development Breast-feeding and immune function

2007

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The newborn receives, via the placenta, maternal IgG antibodies against the microbes present in its surroundings, but such antibodies have a pro-inflammatory action, initiating the complement system and phagocytes. Although the host defence mechanisms of the neonate that involve inflammatory reactivity are somewhat inefficient, this defence system can still have catabolic effects. Breast-feeding compensates for this relative inefficiency of host defence in the neonate by providing considerable amounts of secretory IgA antibodies directed particularly against the microbial flora of the mother and her environment. These antibodies bind the microbes that are appearing on the infant's mucosal membranes, preventing activation of the pro-inflammatory defence. The major milk protein lactoferrin can destroy microbes and reduce inflammatory responses. The non-absorbed milk oligosaccharides block attachment of microbes to the infant's mucosae, preventing infections. The milk may contain anti-secretory factor, which is anti-inflammatory, preventing mastitis in mothers and diarrhoea in infants. Numerous additional factors in the milk are of unknown function, although IL-7 is linked to the larger size of the thymus and the enhanced development of intestinal Tgd lymphocytes in breast-fed compared with non-breast-fed infants. Several additional components in the milk may help to explain why breast-feeding can reduce infant mortality, protecting against neonatal septicaemia and meningitis. It is therefore important to start breast-feeding immediately. Protection is also apparent against diarrhoea, respiratory infections and otitis media. There may be protection against urinary tract infections and necrotizing enterocolitis, and possibly also against allergy and certain other immunological diseases, and tumours. In conclusion, breast-feeding provides a very broad multifactorial anti-inflammatory defence for the infant.

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“…This complex machine secretes virulence proteins in response to sensing the presence of mammalian target cells. Lactoferrin binds to Shigella flexneri [28] and decreases invasiveness of S. flexneri in HeLa cells [29] associated with release and degradation of invasion plasmid antigens B and C, proteins that are responsible for entry of Shigella into mammalian cells [30,31]. Recombinant human lactoferrin also protects rabbits from Shigella flexneri-induced inflammatory enteritis [30].…”

Section: Shigellamentioning

confidence: 99%

Effect of lactoferrin on enteric pathogens

Ochoa

Cleary²

2009

Biochimie

122

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Much has been learned in recent years about the mechanisms by which breastfeeding improves child health and survival. However, there has been little progress in using these insights to improve pediatric care. Factors that are important for protecting the breast fed infant might be expected to decrease the adverse effects of weaning on diarrhea, growth, and development. Lactoferrin, an ironbinding protein with multiple physiological functions (anti-microbial, anti-inflammatory, and immunomodulatory), is one of the most important proteins present in mammalian milk. Protection against gastroenteritis is the most likely biologically relevant activity of lactoferrin. Multiple in vitro and animal studies have shown a protective effect of lactoferrin on infections with enteric microorganisms, including rotavirus, Giardia, Shigella, Salmonella and the diarrheagenic Escherichia coli. Lactoferrin has two major effects on enteric pathogens: it inhibits growth and it impairs function of surface expressed virulence factors thereby decreasing their ability to adhere or to invade mammalian cells. Thus, lactoferrin may protect infants from gastrointestinal infection by preventing the attachment by enteropathogens in the gut. Recently several clinical trials in children have started to address this issue. Whether lactoferrin can prevent a significant portion of diarrheal disease remains to be determined.

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PROTECTIVE ROLE OF HUMAN LACTOFERRIN AGAINST INVASION OF Shigella flexneri M90T. ♦ 707

Cited by 10 publications

References 0 publications

Type III Secretion Systems and Disease

Type III Secretion Systems and Disease

Session 1: Feeding and infant development Breast-feeding and immune function

Effect of lactoferrin on enteric pathogens

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