Haemophilus ducreyi-Induced Interleukin-10 Promotes a Mixed M1 and M2 Activation Program in Human Macrophages

Li, Wei; Katz, Barry P.; Spinola, Stanley M.

doi:10.1128/iai.00912-12

Cited by 44 publications

(52 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Macrophages are dynamic and heterogeneous cells (57). During infection, macrophages are polarized to classically activated M1 cells and alternatively activated M2 cells; macrophages at H. ducreyi-infected sites have mixed M1 and M2 phenotypes (58). Monocyte-derived macrophages polarized to the M2 phenotype take up to 20% of H. ducreyi; up to 4% of the internalized bacteria survive in macrophages 7 h postinfection (58), suggesting that H. ducreyi can resist intracellular killing to some extent.…”

Section: Discussionmentioning

confidence: 99%

Carbon Storage Regulator A Contributes to the Virulence of Haemophilus ducreyi in Humans by Multiple Mechanisms

Gangaiah

Fortney

et al. 2013

Infect Immun

Self Cite

View full text Add to dashboard Cite

The carbon storage regulator A (CsrA) controls a wide variety of bacterial processes, including metabolism, adherence, stress responses, and virulence. Haemophilus ducreyi, the causative agent of chancroid, harbors a homolog of csrA. Here, we generated an unmarked, in-frame deletion mutant of csrA to assess its contribution to H. ducreyi pathogenesis. In human inoculation experiments, the csrA mutant was partially attenuated for pustule formation compared to its parent. Deletion of csrA resulted in decreased adherence of H. ducreyi to human foreskin fibroblasts (HFF); Flp1 and Flp2, the determinants of H. ducreyi adherence to HFF cells, were downregulated in the csrA mutant. Compared to its parent, the csrA mutant had a significantly reduced ability to tolerate oxidative stress and heat shock. The enhanced sensitivity of the mutant to oxidative stress was more pronounced in bacteria grown to stationary phase compared to that in bacteria grown to mid-log phase. The csrA mutant also had a significant survival defect within human macrophages when the bacteria were grown to stationary phase but not to mid-log phase. Complementation in trans partially or fully restored the mutant phenotypes. These data suggest that CsrA contributes to virulence by multiple mechanisms and that these contributions may be more profound in bacterial cell populations that are not rapidly dividing in the human host.

show abstract

Section: Discussionmentioning

confidence: 99%

Carbon Storage Regulator A Contributes to the Virulence of Haemophilus ducreyi in Humans by Multiple Mechanisms

Gangaiah

Fortney

et al. 2013

Infect Immun

Self Cite

View full text Add to dashboard Cite

show abstract

“…In addition to bacterial viability, phagocytosis of H. ducreyi by MDM was required for the optimal production of mature IL-1␤. MDM uptake of nonopsonized or opsonized H. ducreyi is mainly mediated by scavenger receptors (11); approximately 10% to 15% of viable H. ducreyi cells are ingested by MDM (Fig. 3C) (11).…”

Section: Discussionmentioning

confidence: 99%

“…Polarized macrophages express distinct phenotypes and have specialized functions in infection. Recently, we reported that macrophages at H. ducreyiinfected sites exhibit a mixed M1 and M2 activation phenotype and that M2c cells have a higher phagocytic activity against H. ducreyi than M1 cells or nonpolarized macrophages (11). Therefore, we examined the effect of M1 and M2 polarization on H. ducreyi-induced inflammasome activation.…”

Section: Transcriptional Activation Of Inflammasome-related Genes In Hmentioning

confidence: 99%

See 1 more Smart Citation

Haemophilus ducreyi Infection Induces Activation of the NLRP3 Inflammasome in Nonpolarized but Not in Polarized Human Macrophages

Katz

Bauer

et al. 2013

Infect Immun

Self Cite

View full text Add to dashboard Cite

Recognition of microbial infection by certain intracellular pattern recognition receptors leads to the formation of a multiprotein complex termed the inflammasome. Inflammasome assembly activates caspase-1 and leads to cleavage and secretion of the proinflammatory cytokines interleukin-1 beta (IL-1␤) and IL-18, which help control many bacterial pathogens. However, excessive inflammation mediated by inflammasome activation can also contribute to immunopathology. Here, we investigated whether Haemophilus ducreyi, a Gram-negative bacterium that causes the genital ulcer disease chancroid, activates inflammasomes in experimentally infected human skin and in monocyte-derived macrophages (MDM). Although H. ducreyi is predominantly extracellular during human infection, several inflammasome-related components were transcriptionally upregulated in H. ducreyi-in-

show abstract

“…Haemophilus ducreyi [11] It is a gram-negative coccobacillus causing the sexually transmitted disease chancroid, a major cause of genital ulceration in developing countries. It is named for, Agosto Ducrey (1860-1940), (Fig.…”

mentioning

confidence: 99%

Eponyms in the dermatology literature linked to Italy

Aboud¹,

Aboud²

2013

Our Dermatol Online

View full text Add to dashboard Cite

Italy is one of the largest European countries. With 60.8 million inhabitants, it is the fifth most populous country in Europe [1]. It has been ranked as the world's 25th most-developed country and it Quality-of-life Index was ranked in the world's top ten in 2005. Italy enjoys a very high standard of living and has a high public education level [1].It ranks as having the world's 2nd best healthcare system, and the world's 3rd best healthcare performance. Italy had the 12th highest worldwide life expectancy in 2010 [1]. Many of the important dermatology educational resources and periodicals are based in Italy. In Table I [2-16], we listed selected eponyms in dermatology literature linked to Italy.

show abstract

Haemophilus ducreyi-Induced Interleukin-10 Promotes a Mixed M1 and M2 Activation Program in Human Macrophages

Cited by 44 publications

References 50 publications

Carbon Storage Regulator A Contributes to the Virulence of Haemophilus ducreyi in Humans by Multiple Mechanisms

Carbon Storage Regulator A Contributes to the Virulence of Haemophilus ducreyi in Humans by Multiple Mechanisms

Haemophilus ducreyi Infection Induces Activation of the NLRP3 Inflammasome in Nonpolarized but Not in Polarized Human Macrophages

Eponyms in the dermatology literature linked to Italy

Contact Info

Product

Resources

About