American Tegumentary Leishmaniasis is a chronic infection caused by Leishmania protozoan. It is not known whether genetic variances in NOD-like receptor (NLR) family members influence the immune response towards Leishmania parasites and modulate intracellular killing. Using functional genomics, we investigated whether genetic variants in NOD1 or NOD2 influence the production of cytokines by human PBMCs exposed to Leishmania. In addition, we examined whether recognition of Leishmania by NOD2 contributes to intracellular killing. Polymorphisms in the NOD2 gene decreased monocyte- and lymphocyte-derived cytokine production after stimulation with L. amazonensis or L. braziliensis compared to individuals with a functional NOD2 receptor. The phagolysosome formation is important for Leishmania-induced cytokine production and upregulation of NOD2 mRNA expression. NOD2 is crucial to control intracellular infection caused by Leishmania spp. NOD2 receptor is important for Leishmania recognition, the control of intracellular killing, and the induction of innate and adaptive immune responses.
Vaccination against 2019 coronavirus disease (COVID‐19) can reduce disease incidence and severity. Dialysis patients demonstrate a delayed immunologic response to vaccines. We determined factors affecting the immunologic response to COVID‐19 vaccines in haemodialysis patients. All patients within a Swedish haemodialysis network, vaccinated with two doses of COVID‐19 vaccine 2‐8 weeks before inclusion, were eligible for this cross‐sectional study. Severe adult respiratory syndrome coronavirus 2 (SARS‐CoV‐2) spike protein antibody levels were determined by EliA SARS‐CoV‐2‐Sp1 IgG test (Thermo Fisher Scientific, Phadia AB) and related to clinical and demographic parameters. Eighty‐nine patients were included. Patients were vaccinated with two doses of Comirnaty (BNT162b2, 73%) or Spikevax (mRNA‐1273, 23,6%). Three patients received combinations of different vaccines. Response rate (antibody titres >7 U/mL) was 89.9%, while 39.3% developed high antibody titres (>204 U/mL), 47 (43‐50) days after the second dose. A previous COVID‐19 infection associated with higher antibody titres (median (25th‐75th percentile) 1558.5 (814.5‐3,763.8) U/mL vs 87 (26‐268) U/mL, P = .002), while time between vaccine doses did not differ between groups (P = .7). Increasing SARS‐CoV‐2 antibody titres were independently associated with increasing time between vaccine doses (B 0.241, P = .02), decreasing serum calcium levels (B −0.233, P = .007) and previous COVID‐19 (B 1.078, P < .001). In conclusion, a longer interval between COVID‐19 mRNA vaccine doses, lower calcium and a previous COVID‐19 infection were independently associated with a stronger immunologic vaccination response in haemodialysis patients. While the response rate was good, only a minority developed high antibody titres, 47 (43‐50) days after the second vaccine dose.
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