Haemophilus ducreyi Elicits a Cutaneous Infiltrate of CD4 Cells during Experimental Human Infection

Spinola, Stanley M.; Orazi, Attilio; Arno, Janet N.; Fortney, Kate R.; Kotylo, Patricia K.; Chen, Cheng‐Yen; Campagnari, Anthony A.; Hood, Antoinette F.

doi:10.1093/infdis/173.2.394

Cited by 116 publications

(192 citation statements)

References 37 publications

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“…However, APC within peripheral tissue, such as cervix, do not normally function in antigen presentation in situ, but mature into an APC phenotype only after migration to lymph nodes or spleen. Increased numbers of 'activated' Langerhans cells outside lymphoid tissue are only found during chronic or persistent immunological responses [6,7].…”

Section: Introductionmentioning

confidence: 99%

“…In contrast to the HPV-related pattern of migration and activation, persistent immune responses, e.g. associated with chronic infection, are often associated with increased numbers of Langerhans cells with an activated or mature phenotype [6,7]. The phenotype of the Langerhans cells within CIN lesions is therefore suggestive of only limited immune activation within these lesions.…”

mentioning

confidence: 99%

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The antigen-presenting environment in normal and human papillomavirus (HPV)-related premalignant cervical epithelium

Mota

Rayment

Chong

et al. 1999

Clinical and Experimental Immunology

116

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SUMMARYThe activation of HPV-specific T cells within the cervical microenvironment is likely to play an important part in the natural history of cervical intraepithelial neoplasia (CIN). The extent and the type of T cell activation will depend critically on the expression of MHC, costimulatory cell surface molecules and cytokines by keratinocytes and Langerhans cells within the cervical lesion. Expression of MHC class II (HLA-DR and -DQ), costimulatory/adhesion molecules (CD11a/18, CD50, CD54, CD58 and CD86) and cytokines (tumour necrosis factor-alpha (TNF-a) and IL-10) was therefore investigated by immunohistochemistry in normal squamous epithelium (n ¼ 12), low-grade (n ¼ 23) and high-grade (n ¼ 18) squamous intraepithelial lesions of the cervix. CIN progression was associated with de novo expression of HLA-DR and CD54, and increased expression of CD58 by keratinocytes. However, significantly, there was no expression of any adhesion/costimulation molecule by epithelial Langerhans cells in any cervical biopsy studied. Furthermore, TNF-a, a potent activator of Langerhans cells, was expressed constitutively by basal keratinocytes in normal cervix (12þ/12), but expression of this cytokine was absent in a number of CIN samples (20þ/23 for low-grade, 12þ/18 for high-grade CIN). Conversely, the suppressive cytokine IL-10 was absent in normal epithelium (0þ/12), but was upregulated in a number of CIN lesions (12þ/23 for low-grade, 8þ/18 for high-grade CIN). The restricted expression of costimulation/adhesion molecules and the nature of the cytokine microenvironment within the epithelium may act to limit effective immune responses in some CIN lesions.

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Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

The antigen-presenting environment in normal and human papillomavirus (HPV)-related premalignant cervical epithelium

Mota

Rayment

Chong

et al. 1999

Clinical and Experimental Immunology

116

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“…In one experiment, a triply charged precursor ion with [M ϩ 2H ϩ Na] 3ϩ at m/z 814.61 3ϩ was selected that corresponds to an oligosaccharide species containing (LacNAc) 3 Although ESI-MS/MS spectra provided complete sequences of the terminal LacNAc regions of all oligosaccharides that were isolated, a different approach was needed to obtain sequence data on oligosaccharide branches from low abundant LOS-glycoforms and/or ones that contain sialic acid. In these cases, isolation of the corresponding oligosaccharides was difficult, especially for those that contain sialic acid.…”

Section: Resultsmentioning

confidence: 99%

“…Although chancroid is uncommon in the United States, it is prevalent in many developing countries worldwide [1]. Chancroid has also been shown to be a significant risk factor for transmission of human immunodeficiency virus (HIV) [2][3][4]. Recently, the number of H. ducreyi clinical isolates with antibiotic resistance has increased [1,5], suggesting that this sexually transmitted disease is far from contained and represents a growing threat to world health.…”

mentioning

confidence: 99%

Characterization of lipooligosaccharides from Haemophilus ducreyi containing polylactosamine repeats

Schilling

Gibson

Filiatrault

et al. 2002

J. Am. Soc. Mass Spectrom.

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Haemophilus ducreyi, a gram-negative human mucosal pathogen, is one of the principal causes of genital ulcer disease. The lipooligosaccharides (LOS) of these bacteria are considered to be a major virulence factor and have been implicated in the adherence and invasion of H. ducreyi to several human cell types. An isogenic heptosyltransferase-III knockout strain (waaQ) was recently constructed from H. ducreyi 35000 wild-type strain and immunochemical and molecular weight data of the isolated LOS suggested the presence of poly-N-acetyllactosamine (LacNAc) (Filiatrault et al., Infect. Immun. 2000, 68, 3352-3361). In this present study, the structures of these novel LOS-glycoforms were characterized by matrix-assisted laser desorption/ionization (MALDI) and electrospray ionization (ESI) mass spectrometry in combination with exoglycosidase digestion. Detailed structural information was obtained for the oligosaccharide (OS) portions of these LOS showing between one to five linear LacNAc repeats on the non-reducing terminus of the main oligosaccharide branch. When grown on solid media, the organism produced LacNAc repeats that were further modified by the addition of sialic acid. Enzymatic digestion with ␤-galactosidase, ␤-N-acetylhexosaminidase, and neuraminidase type VI-A yielded truncated glycoforms consistent with a polyLacNAc structure capped at various end points with sialic acid. ESI-MS/MS mass spectrometry on a quadrupole time-offlight instrument was particularly effective in obtaining detailed structural information on the least abundant, high-mass glycoforms. Although LOS containing terminal di-LacNAc have been reported, this is the first time to our knowledge that a linear polyLacNAc structure has been characterized in bacteria. (J Am Soc Mass Spectrom 2002, 13, 724 -734)

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“…In addition, this pathogen poses a significant risk factor for the transmission of HIV (2,3). The lipooligosaccharide (LOS) of H. ducreyi is considered a major virulence factor and has been implicated in the adherence of H. ducreyi to human foreskin fibroblasts and keratinocytes (4,5).…”

mentioning

confidence: 99%

Metabolic incorporation of unnatural sialic acids into Haemophilus ducreyi lipooligosaccharides

Goon

Schilling

Tullius

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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The lipooligosaccharides (LOS) of Haemophilus ducreyi are highly sialylated, a modification that has been implicated in resistance to host defense and in virulence. In previous work, we demonstrated that H. ducreyi scavenges sialic acid from the extracellular milieu and incorporates those residues into LOS. Here we report that H. ducreyi can use unnatural sialic acids bearing elongated N-acyl groups from three to seven carbon atoms in length, resulting in outer membrane presentation of unnatural sialyl-LOS. The unnatural variant comprises Ϸ90% of cell surface sialosides when exogenous substrates are added to the media at micromolar concentrations, despite the availability of natural sialic acid in the growth media. Although they represent the majority of cell surface sialosides, analogs with longer N-acyl groups diminish the overall level of LOS sialylation, culminating in complete inhibition of LOS sialylation by N-octanoyl sialic acid. Thus, sialylation of H. ducreyi LOS can be modulated with respect to the structure of the terminal sialic acid residue and the extent to which the LOS acceptor is modified by supplying the bacteria with various sialic acid analogs.

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Haemophilus ducreyi Elicits a Cutaneous Infiltrate of CD4 Cells during Experimental Human Infection

Cited by 116 publications

References 37 publications

The antigen-presenting environment in normal and human papillomavirus (HPV)-related premalignant cervical epithelium

The antigen-presenting environment in normal and human papillomavirus (HPV)-related premalignant cervical epithelium

Characterization of lipooligosaccharides from Haemophilus ducreyi containing polylactosamine repeats

Metabolic incorporation of unnatural sialic acids into Haemophilus ducreyi lipooligosaccharides

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