Changing Epidemiology of Gonorrhea in Adelaide, South Australia.

BACKGROUND: Gonorrhea is a significant public health concern. The changing epidemiology of gonorrhea in Australia has highlighted the need for detailed examination of surveillance data to determine population groups at greatest risk for infection. METHODS: We analyzed deidentified gonorrhea notification data for the years 2012 to 2017, in Adelaide (N = 3680), calculating age-adjusted notification and antibiotic resistance rates. Age, gender, year, sexual orientation, and socioeconomic status were assessed for associations with gonorrhea notifications using negative binomial, log binomial and spatial autoregressive models. Maps were generated to examine spatial localization of gonorrhea rates in Adelaide. RESULTS: Gonorrhea notification rates in Adelaide increased annually, with a 153% adjusted increase in rates from 2012 to 2017, localized to specific areas and inversely associated with income levels. The increase in rates in 2016 and 2017 was associated with young heterosexuals from low income areas. Azithromycin-resistant notifications increased significantly in 2016 in young heterosexuals. Reinfections were significantly more likely in men who have sex with men than other population groups. CONCLUSIONS: This study demonstrates the changing epidemiology of gonorrhea in Adelaide from a largely men who have sex with men profile toward an increase in young heterosexual gonorrhea. This could be seen as a harbinger for future increases in heterosexually transmitted HIV and other sexually transmitted infections in Australia.

Opposing roles for CXCR3 signaling in central nervous system versus ocular inflammation mediated by the astrocyte-targeted production of IL-12.

CXCR3 and its ligands are important for the trafficking of activated CD4(+) T(H)1 T cells, CD8(+) T cells, and natural killer cells during inflammation. Recent functional studies demonstrate a more diverse role of CXCR3 in inflammatory diseases of the central nervous system (CNS). We examined the impact of CXCR3 on a less complex interferon-γ-dependent, type 1 cell-mediated immune response in the CNS, induced in mice by the transgenic production of glial fibrillary acidic protein IL-12 (GF-IL12) by astrocytes and retinal Müller cells. GF-IL12 mice develop ataxia because of severe cerebellar inflammation but have little overt ocular disease. Surprisingly, CXCR3-deficient GF-IL12 mice (GF-IL12/CXCR3KO) have drastically reduced ataxia but developed cataracts, severe ocular inflammation, and eye atrophy. Most GF-IL12/CXCR3KO mice had minimal cerebellar inflammation but severe retinal disorganization, loss of photoreceptors, and lens destruction in the eye. The number of CD3(+), CD11b(+), and natural killer 1.1(+) cells were reduced in the CNS but highly increased in the eyes of GF-IL12/CXCR3KO compared with GF-IL12 mice. High levels of interferon-γ, IL-1, tumor necrosis factor α, CXCL9, CXCL10, and CCL5 were found in GF-IL12 cerebelli and GF-IL12/CXCR3KO eyes. Our findings demonstrate key but paradoxical functions for CXCR3 in IL-12-induced immune disease in the CNS, promoting inflammation in the brain yet restricting it in the eye. We conclude that the function of CXCR3 in cellular immune disease is driven by a common trigger and is controlled by tissue-specific factors.

The cell-specific induction of CXC chemokine ligand 9 mediated by IFN-gamma in microglia of the central nervous system is determined by the myeloid transcription factor PU.1.

The IFN-gamma-inducible chemokines CXCL9 and CXCL10 are implicated in the pathogenesis of T cell-mediated immunity in the CNS. However, in various CNS immune pathologies the cellular localization of these chemokines differs, with CXCL9 produced by macrophage/microglia whereas CXCL10 is produced by both macrophage/microglia and astrocytes. In this study, we determined the mechanism for the microglial cell-restricted expression of the Cxcl9 gene induced by IFN-gamma. In cultured glial cells, the induction of the CXCL9 (in microglia) and CXCL10 (in microglia and astrocytes) mRNAs by IFN-gamma was not inhibited by cycloheximide. Of various transcription factors involved with IFN-gamma-mediated gene regulation, PU.1 was identified as a constitutively expressed NF in microglia but not in astrocytes. STAT1 and PU.1 bound constitutively to the Cxcl9 gene promoter in microglia, and this increased significantly following IFN-gamma treatment with IFN regulatory factor-8 identified as an additional late binding factor. However, in astrocytes, STAT1 alone bound to the Cxcl9 gene promoter. STAT1 was critical for IFN-gamma induction of both the Cxcl9 and Cxcl10 genes in microglia and in microglia and astrocytes, respectively. The small interfering RNA-mediated knockdown of PU.1 in microglia markedly impaired IFN-gamma-induced CXCL9 but not STAT1 or IFN regulatory factor-8. Cells of the D1A astrocyte line showed partial reprogramming to a myeloid-like phenotype posttransduction with PU.1 and, in addition to the expression of CD11b, acquired the ability to produce CXCL9 in response to IFN-gamma. Thus, PU.1 not only is crucial for the induction of CXCL9 by IFN-gamma in microglia but also is a key determinant factor for the cell-specific expression of this chemokine by these myeloid cells.