α-Defensins in the gastrointestinal tract

Cunliffe, Robert

doi:10.1016/s0161-5890(03)00157-3

Cited by 147 publications

(125 citation statements)

References 29 publications

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“…7,51 The remaining 2 human defensins (HD), HD-5 and HD-6, are expressed in the intestinal Paneth cells and probably contribute to innate defense mechanisms of the intestinal mucosal surface. 52 Thus, it is conceivable that ␣-defensins exert anti-HIV activity mainly at the mucosal level and at sites of active inflammation, where they can reach considerable levels, rather than in blood, where they are diluted and rapidly inactivated by plasmatic proteins. It has been estimated that 10 6 neutrophils contain approximately 5 g ␣-defensins, which translates into a cellular concentration above 10 mg/mL.…”

Section: Discussionmentioning

confidence: 99%

α-defensins block the early steps of HIV-1 infection: interference with the binding of gp120 to CD4

Furci¹,

Sironi²,

Tolazzi³

et al. 2006

Blood

102

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␣-defensins are antibiotic peptides that act as natural inhibitors of HIV-1 infection. However, the mechanisms of such inhibition are still unclear. Here we demonstrate that ␣-defensins block the earliest steps in the viral infectious cycle, as documented using an HIV-1 envelopemediated cell-fusion assay. A broad-spectrum inhibitory activity was observed on primary and laboratory-adapted HIV-1 isolates irrespective of their coreceptor specificity and genetic subtype. A primary mechanism of such inhibition was identified as the ability of ␣-defensins to bind specifically both to the primary HIV-1 cellular receptor, CD4, and to the viral envelope glycoprotein, gp120. Moreover, treatment of CD4 ؉ T cells with ␣-defensins caused a dramatic downmodulation of CD4 expression. By monoclonal antibody competition, the regions of interaction with ␣-defensins were mapped to the D1 domain of CD4 and to a surface contiguous to the CD4-and coreceptorbinding sites of gp120. Consistent with these findings, ␣-defensins inhibited the binding of gp120 to CD4. These data demonstrate that ␣-defensins specifically block the initial phase of the HIV infectious cycle and modulate the expression of CD4, a critical receptor in the physiology of T-cell activation. IntroductionEvidence suggests that a concerted action of innate and adaptive immune responses is essential for the effective containment and, ultimately, the clearance of invading microorganisms. 1 The innate immune system is phylogenetically more archaic and constitutes the first line of antimicrobial defense, characterized by a rapid response time; however, it is limited in its target specificity. By contrast, the adaptive immune system has evolved refined molecular devices for the recognition of a wide variety of specific epitopes, but a lag time is required for its functional activation. Once activated, most of the cells involved in both innate and cognate immune responses secrete soluble factors, including cytokines, chemokines, antibiotic peptides, and others, which can directly antagonize infectious microorganisms and/or contribute to the recruitment and activation of other immune cells, thereby amplifying the cascade of defense mechanisms and bolstering their effectiveness. 2,3 In HIV infection, various host-derived soluble factors with antiviral activity have been described, which act by both specific and nonspecific mechanisms. These include chemokines such as RANTES, MIP-1␣, and MIP-1␤ 4 ; cytokines such as the interferons, IL-10, IL-13, IL-16, transforming growth factor-␤, and others 5 ; as well as, more recently, defensins. [6][7][8][9] Defensins are natural antibiotic peptides that play an important role in innate immune responses by acting as broad-spectrum antibacterial, antifungal, and antiviral effector molecules 10 as well as by enhancing certain adaptive immune responses. 11 ␣-defensins 1 to 3 are 3-to 4-kDa cationic peptides (29 to 30 amino acids [aa]) characterized by a conserved 6-cysteine motif, with 3 disulfide bonds that impose a characteristic ␤-sheet ...

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Section: Discussionmentioning

confidence: 99%

α-defensins block the early steps of HIV-1 infection: interference with the binding of gp120 to CD4

Furci¹,

Sironi²,

Tolazzi³

et al. 2006

Blood

102

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“…The slime layer of the intestinal mucosa has a barrier function to the S. enteritidis; moreover pankrin, bile salt and small intestinal juice can depress the bacterium. Some studies suggest that the gene encoding the invasive protein is depressed because of the bile [19,20] . Meanwhile, the involvement of mucosal IgA in the protection against S. enteritidis involving the epithelial surface has been reported [21,22] .…”

Section: The Value Of S Enteritidis Infections From Other Viral Infementioning

confidence: 99%

Application of an indirect immunofluorescent staining method for detection of Salmonella enteritidis in paraffin slices and antigen location in infected duck tissues

Yan

Cheng²,

Wang³

et al. 2008

WJG

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CONCLUSION:IFA is an intuitionist, sensitive and specific method in detecting S. enteritidis antigen in paraffin wax slices, and it is a good method in diagnosis and antigen location of S. enteritidis . We also conclude that the gland of Garder, heart, kidney, spleen, liver, ileum, jejunum are target organs in S. enteritidis infections of duck, and S. enteritidis is an intracellular parasitic bacterium. INTRODUCTIONSalmonella enteritidis (S. enteritidis) is the infectious disease causing Zoonoses. S. enteritidis is one of the primary causes of human food poisoning throughout the world, and has become a pointed public health problem [1][2][3][4] . China is the biggest country in the raising and consumption of duck in the world, but the S. enteritidis bacillus infection is a severely important infectious disease in the duck industry [5] . S. enteritidis outbreaks have been found to be associated with the consumption of contaminated and undercooked poultry products, such as eggs and egg-containing products, and have become a serious economic and public health problem [6] . Conventional methods for isolation of S. enteritidis are too laborious, not sufficiently sensitive or correct [7,8] . To our knowledge, a serum method for detection and antigen location of S. enteritidis has not been reported. Thus, to establish a rapid, sensitive and highly specific in paraffin slices and antigen location in infected duck tissues. METHODS:Rabbits were immunized with purified bacillus to obtain S. enteritidis -specific antibody, which were then extracted by the caprylic-ammonium sulphate method, purified through High-Q columns. An indirect immuno-fluorescent staining method (IFA) was established to detect the S. enteritidis antigen in paraffin slices. S. enteritidis was detected in each organ tissue of ducklings experimentally infected with S. enteritidis . RESULTS:The gland of Garder, heart, kidney, spleen, liver, brain, ileum, jejunum, bursa of Fabricius from S. enteritidis experimentally infected ducklings were positive or strongly positive, and the S. enteritidis antigen was mainly distributed in the infected cell cytoplasm.

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“…Structurally, the difference between the two defensins lies within the length of peptide segments between the six cysteines and pairing of the cysteines (Bals and Wilson 2003). Six different human alphadefensins have been identified so far, including four human neutrophil peptides, HNP1-4, and two others known as human defensins 5 and 6 (HD-5, HD-6) (Ganz, Selsted et al 1985;Ganz and Lehrer 1994;Cunliffe 2003). Alpha-defensins are arginine-rich and localized in either neutrophil azurophilic granules or Paneth cells, which are the epithelia of the intestinal mucosa.…”

Section: Alpha-defensinsmentioning

confidence: 99%