HIV‐infected individuals have an increased risk of invasive bacterial infections, even at early clinical stages with relatively normal CD4+ T‐cell counts. The pathogenic mechanisms behind this are not fully understood. However, an increasing number of studies indicate that HIV may impair the innate immunity to bacteria by infecting key cells of the monocyte/macrophage lineage. In this study, the effects of HIV infection on the protein profile of undifferentiated monocyte‐like THP‐1 cells were examined by a mass spectrometric approach based on stable isotope labelling with amino acid in cell culture (SILAC). We identified 651 proteins, of which nine proteins were down‐regulated and 17 proteins were up‐regulated in HIV‐infected THP‐1 cells as compared to uninfected controls. Most remarkably, the IL‐1 receptor associated kinase 4 (IRAK‐4), which is essential for virtually all TLR signalling, was suppressed, whereas the precursor for the antibiotic peptide Dermcidin was up‐regulated in HIV‐infected cells. Upon stimulation of either TLR2 or TLR4, the HIV‐infected THP‐1 cells displayed reduced TNF‐α secretion. The HIV‐induced down‐regulation of IRAK‐4 was reconfirmed in monocyte‐derived macrophage cell cultures. These data suggests that HIV may impair the TLR signalling cascade for pathogen recognition in cells of the monocyte/macrophage lineage and thus, may reduce the ability of the innate immune system to sense invading pathogens and initiate appropriate responses.
Background
The knowledge regarding the occurrence and the clinical implications of tick-borne infections in immunosuppressed patients living in tick-endemic areas is limited.
Methods
Adult patients with autoimmune conditions requiring immunosuppressive treatment such as infliximab and rituximab, were invited to participate in the study when they attended the hospital for treatment and/or control of the disease. Whole blood samples were analysed by real-time PCR for Borrelia burgdorferi s.l., Borrelia miyamotoi, Anaplasma phagocytophilum, Rickettsia spp., Candidatus Neoehrlichia mikurensis and Babesia spp.
Results
The occurrence of tick-borne pathogens in the blood of patients (n=163) with autoimmune conditions requiring immunosuppressive treatment were evaluated. Pathogen DNA was detected in 8.6% (14/163) of the patients. The predominant pathogen was Candidatus Neoehrlichia mikurensis (12/14), which was carried in the blood of infected patients for 10-59 days until treatment with doxycycline. Borrelia burgdorferi sensu lato and Rickettsia spp. were detected in one patient each. The B. burgdorferi-infected patient presented with fever, whereas the remaining patients were judged to have subclinical infections. Borrelia miyamotoi, Anaplasma phagocytophilum, and Babesia spp. were not detected in any patient.
Conclusions
Patients treated with biologicals and living in a tick-endemic area seem to have a high risk of contracting Ca. Neoehrlichia mikurensis infection which if left untreated could result in thromboembolic complications.
Clinician diagnosed 85% with NCGS. The proportion of NCGS was lower according to the Salerno and Monash cut-offs. The Salerno cut-off should be the starting point for a common definition of symptom change.
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