Experimental Infection withHaemophilus ducreyiin Persons Who Are Infected with HIV Does Not Cause Local or Augment Systemic Viral Replication

Abstract

We infected 11 HIV-seropositive volunteers whose CD4(+) cell counts were >350 cells/ microL (7 of whom were receiving antiretrovirals) with Haemophilus ducreyi. The papule and pustule formation rates were similar to those observed in HIV-seronegative historical control subjects. No subject experienced a sustained change in CD4(+) cell count or HIV RNA level. The cellular infiltrate in biopsy samples obtained from the HIV-seropositive and HIV-seronegative subjects did not differ with respect to the percentage of leukocytes, neutrophils, macrophages, or T cells. The CD4(+):CD8(+) cell ratio in biopsy samples from the HIV-seropositive subjects was 1:3, the inverse of the ratio seen in the HIV-seronegative subjects (P<.0001). Although CD4(+) cells proliferated in lesions, in situ hybridization and reverse-transcription polymerase chain reaction for HIV RNA was negative. We conclude that experimental infection in HIV-seropositive persons is clinically similar to infection in HIV-seronegative persons and does not cause local or augment systemic viral replication. Thus, prompt treatment of chancroid may abrogate increases in viral replication associated with natural disease.

Haemophilus ducreyi Partially Activates Human Myeloid Dendritic Cells

“…How H. ducreyi is taken up by DC is under investigation in our laboratory. DC ingested and killed H. ducreyi, but killing was incomplete as 5% of the internalized bacteria were recovered from DC for up to 48 h. In pustules induced by experimental inoculation, some DC express the maturation markers CD83 and DC-LAMP, but the majority of DC are immature CD1a-positive cells (20). H. ducreyi-specific T-cell lines are recovered from pustules of volunteers who are infected for 7 to 14 days (9).…”

“…Microbial pathogens employ multiple strategies to subvert DC function, such as the impairment of DC maturation, cytokine secretion, or migration and the induction of DC apoptosis or necrosis (1,4,12,21,34,45). In human volunteers who are experimentally infected with H. ducreyi, CD83-positive and DC lysosome-associated membrane protein (DC-LAMP)-positive cells are found in the epidermis or dermis of pustules (20). However, immature CD1a-positive cells are more abundant in experimental lesions than are cells that express CD83 and DC-LAMP (20), suggesting that H. ducreyi may not fully promote DC maturation.…”

“…In human volunteers who are experimentally infected with H. ducreyi, CD83-positive and DC lysosome-associated membrane protein (DC-LAMP)-positive cells are found in the epidermis or dermis of pustules (20). However, immature CD1a-positive cells are more abundant in experimental lesions than are cells that express CD83 and DC-LAMP (20), suggesting that H. ducreyi may not fully promote DC maturation.…”

Infectious Diseases and Infestations of the Vulva

“…The infection is found mainly in developing and third-world countries [ 87 -89 ]. Chancroid produces a 25-fold increased HIV acquisition and transmission rate [ 89 ]. Very few people are diagnosed in the United States each year with this infection.…”

Dysregulated Immune Profiles for Skin and Dendritic Cells Are Associated with Increased Host Susceptibility toHaemophilus ducreyiInfection in Human Volunteers

“…In pustules obtained from subjects infected once, the ratio of myeloid dendritic cells (DC) to plasmacytoid DC is 2.8-fold that in peripheral blood (5a). DC-LAMP-and CD83-positive cells are present in the epidermis and dermis of pustules (36), indicating that DC maturation occurs in response to infection. In pustules, H. ducreyi is surrounded by PMN and macrophages but is not ingested (7), indicating that evasion of phagocytosis is a major mechanism of bacterial survival (3,35,50,78,84).…”