Acute Sexually Transmitted Infections Increase Human Immunodeficiency Virus Type 1 Plasma Viremia, Increase Plasma Type 2 Cytokines, and Decrease CD4 Cell Counts

Anzala, Aggrey O.; Simonsen, J. Neil; Kimani, Joshua; Ball, T. Blake; Nagelkerke, Nico; Rutherford, John D.; Ngugi, Elizabeth; Bwayo, Job J.; Plummer, Francis A.

doi:10.1086/315733

Cited by 79 publications

(63 citation statements)

References 25 publications

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“…gonorrhoeae infections have been suggested to downregulate mucosal immune defenses in order to promote bacterial survival in the human host. Recent work has linked gonococcal cervicitis to decreases in T-cell populations thought to increase HIV susceptibility and disease progression (3). Studies have also shown that interactions between opacity protein-expressing gonococci and the carcinoembryonic antigenrelated cellular adhesion molecule on immune cell surfaces inhibit T-cell responses (7) and induce B-cell apoptosis, halting antibody production (41).…”

Section: Discussionmentioning

confidence: 99%

“…To determine if portions of PilE can suppress immune-cell responses, we conducted suppressor cell assays evaluating the direct and indirect effects of DQ and re-Pilin on B-and T-cell responses. If binding of pilin proteins to immune cell surfaces could activate T-reg cells during gonococcal cervicitis, these cells would inhibit other T-cell responses, accounting for decreases in CD4 ϩ and CD8 ϩ cells (3). Neither the addition of exogenous DQ or re-Pilin nor that of spleen cells isolated after DQ or re-Pilin immunization suppresses Tor B-cell populations (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Gonococcal cervicitis also increases human immunodeficiency virus (HIV) susceptibility and accelerates HIV disease progression (3). Prior to 2004, gonorrhea infections were commonly treated with broad-spectrum antibiotics from the fluoroquinolone and cephalosporin classes, but the emergence of fluoroquinolone-resistant N. gonorrhoeae isolates in the United States has led to the recommendation that the use of fluoroquinolones for the treatment of gonococcal cases be discontinued (11).…”

mentioning

confidence: 99%

“…These additional experiments were motivated by the observation that during HIV infections, gonococcal cervicitis causes transient decreases in CD4 ϩ and CD8 ϩ T-cell counts (3,31). Piliated gonococci may modulate initial CD4 ϩ T-cell proliferation, thereby inducing secretion of interleukin-10 (IL-10), a T regulatory (T-reg) cell activator.…”

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confidence: 99%

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Conserved Regions fromNeisseria gonorrhoeaePilin Are Immunosilent and Not Immunosuppressive

et al. 2007

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PilE is the primary subunit of type IV pili from Neisseria gonorrhoeae and contains a surface-exposed hypervariable region thought to be one feature of pili that has prevented development of a pilin-based vaccine. We have created a three-dimensional structure-based antigen by replacing the hypervariable region of PilE with an aspartate-glutamine linker chosen from the sequence of Pseudomonas aeruginosa PilA. We then characterized murine immune responses to this novel protein to determine if conserved PilE regions could serve as a vaccine candidate. The control PilE protein elicited strong T-cell-dependent B-cell responses that are specific to epitopes in both the hypervariable deletion and control proteins. In contrast, the hypervariable deletion protein was unable to elicit an immune response in mice, suggesting that in the absence of the hypervariable region, the conserved regions of PilE alone are not sufficient for antibody production. Further analysis of these PilE proteins with suppressor cell assays showed that neither suppresses T-or B-cell responses, and flow cytometry experiments suggested that they do not exert suppressor effects by activating T regulatory cells. Our results show that in the murine model, the hypervariable region of PilE is required to activate immune responses to pilin, whereas the conserved regions are unusually nonimmunogenic. In addition, we show that both hypervariable and conserved regions of pilin are not suppressive, suggesting that PilE does not cause the decrease in T-cell populations observed during gonococcal cervicitis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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confidence: 99%

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Conserved Regions fromNeisseria gonorrhoeaePilin Are Immunosilent and Not Immunosuppressive

et al. 2007

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“…Symptomatic Ng infection is associated with increased detection of viral-derived nucleic acids from genital secretions of men and women (11)(12)(13), and this effect was reversed upon successful Ng treatment. Concurrent Ng infection is associated with an increase in HIV-1 viremia (14,15), decreases in HIV-1 target lymphocyte [cluster of differentiation 4-positive (CD4 + ) T-cell] counts (14), and a decrease in effector [cluster of differentiation 8-positive (CD8 + ) T-cell] lymphocyte responses (16). Because of the impact of Ng on HIV-1 shedding, coinfection is associated with a two-to fivefold increase in male-to-female transmission rates (3).…”

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confidence: 99%

Neisseria gonorrhoeae-derived heptose elicits an innate immune response and drives HIV-1 expression

Malott¹,

Keller

Gaudet³

et al. 2013

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

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Clinical and epidemiological synergy exists between the globally important sexually transmitted infections, gonorrhea and HIV. Neisseria gonorrhoeae , which causes gonorrhea, is particularly adept at driving HIV-1 expression, but the molecular determinants of this relationship remain undefined. N. gonorrhoeae liberates a soluble factor that potently induces expression from the HIV-1 LTR in coinfected cluster of differentiation 4-positive (CD4 + ) T lymphocytes, but this factor is not a previously described innate effector. A genome-wide mutagenesis approach was undertaken to reveal which component(s) of N. gonorrhoeae induce HIV-1 expression in CD4 + T lymphocytes. A mutation in the ADP-heptose biosynthesis gene, hldA , rendered the bacteria unable to induce HIV-1 expression. The hldA mutant has a truncated lipooligosaccharide structure, contains lipid A in its outer membrane, and remains bioactive in a TLR4 reporter-based assay but did not induce HIV-1 expression. Mass spectrometry analysis of extensively fractionated N. gonorrhoeae- derived supernatants revealed that the LTR-inducing fraction contained a compound having a mass consistent with heptose-monophosphate (HMP). Heptose is a carbohydrate common in microbes but is absent from the mammalian glycome. Although ADP-heptose biosynthesis is common among Gram-negative bacteria, and heptose is a core component of most lipopolysaccharides, N. gonorrhoeae is peculiar in that it effectively liberates HMP during growth. This N. gonorrhoeae- derived HMP activates CD4 + T cells to invoke an NF-κB–dependent transcriptional response that drives HIV-1 expression and viral production. Our study thereby shows that heptose is a microbial-specific product that is sensed as an innate immune agonist and unveils the molecular link between N. gonorrhoeae and HIV-1.

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Cervico‐vaginal dysplasia—papillomavirus‐induced and HIV‐1 infection: role of correlated markers for prognostic evaluation

Pugliese

Andronico

Gennero

et al. 2002

Cell Biochemistry & Function

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Sexually-transmitted diseases (STD) can facilitate the progression of HIV-1 infection. Among them, as we have previously demonstrated, cervico-vaginal dysplasia-papillomavirus (HPV)-induced, together with HSV-2 co-infection, seems to be correlated with a more evident immunodepression in HIV-positive women, compared with other sexually transmitted diseases. Here we have analysed some of the main correlated markers of HIV-1 infection progression: CD4 + T lymphocyte concentration, CD4 +/CD8 + T cells ratio, HIV-1 RNA loads and haemoglobin (Hb) concentration in 30 HIV-1 positive women co-infected with HPV, and suffering from cervico-vaginal dysplasia, in different stages. In particular, we noticed a positive correlation, evaluated by Spearman's test, between the degree of progression of dysplastic stages (CIN1 --> 3) until invasive carcinoma (IC) and HIV-1 RNA loads (C(s) = +0.78; p < 0.001), and in contrast, a negative correlation between the same stages of progression and respectively CD4 + T cell concentration (C(s) = -0.54; p = 0.01), ratio (C(s) = - 0.63; p = 0.002) and Hb concentration (C(s) = -0.85; p < 0.001). In conclusion, it is important to underline that low levels of Hb generally paralleled the degree of immunodepression. In fact CD4 + T cell levels and ratio positively correlated with Hb concentrations respectively, with C(s) = + 0.83; p < 0.001 and C(s) = + 0.90; p < 0.001. Finally, the most efficacious antiretroviral combined therapy (HAART = Highly Active Antiretroviral Therapy) can improve the above described laboratory parameters in HIV-1/HPV co-infected women and seems to prevent the progression of CIN1 to the following stages of the dysplastic disease.

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Acute Sexually Transmitted Infections Increase Human Immunodeficiency Virus Type 1 Plasma Viremia, Increase Plasma Type 2 Cytokines, and Decrease CD4 Cell Counts

Cited by 79 publications

References 25 publications

Conserved Regions fromNeisseria gonorrhoeaePilin Are Immunosilent and Not Immunosuppressive

Conserved Regions fromNeisseria gonorrhoeaePilin Are Immunosilent and Not Immunosuppressive

Neisseria gonorrhoeae-derived heptose elicits an innate immune response and drives HIV-1 expression

Cervico‐vaginal dysplasia—papillomavirus‐induced and HIV‐1 infection: role of correlated markers for prognostic evaluation

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