TREM-1 Expression on the Surface of Neutrophils in Patients With Visceral Leishmaniasis Is Associated With Immunopathogenesis.

Visceral leishmaniasis (VL) is a systemic chronic and potentially fatal disease for humans. Mechanisms related to the dysregulation of the inflammatory response may be involved in both the pathogenesis and prognosis of VL. Triggering Receptor Expressed on Myeloid Cells-1 (TREM-1) is a receptor constitutively expressed on neutrophils and monocyte subsets. The protein serves to regulate and amplify inflammatory responses. This study aimed to evaluate the expression profile of TREM-1 on the surface of neutrophils from patients with VL at varying time points during leishmanicidal treatment. For this purpose, neutrophils were isolated from the peripheral blood of patients with VL at different stages of treatment, which include 0, 7, and 30 days after treatment. Surface TREM-1 expression was assessed by immunophenotyping neutrophil populations. In addition, the association of TREM-1 expression on the surface of neutrophils with clinical and laboratory parameters and serum levels of inflammatory mediators was also evaluated. Results demonstrate a lower surface expression of TREM-1 in VL patients in the absence of treatment. However, increased levels of TREM-1 expression were observed 7 and 30 days after the start of treatment, with levels similar to those of healthy controls. TREM-1 expression was directly correlated with lymphocyte and erythrocyte count and indirectly correlated with spleen and liver size. Furthermore, elevated levels of TREM-1 expression were also correlated with lower serum levels of interleukin (IL)-22. Taken together, these results suggest that infection by Leishmania infantum leads to depressed TREM-1 expression on the neutrophil surface and may contribute to the inflammatory imbalance that characterizes active VL disease.

Niacin metabolite excretion in alcoholic pellagra and AIDS patients with and without diarrhea.

OBJECTIVE: Malnourished patients with the acquired immunodeficiency syndrome (AIDS) can develop pellagra-like manifestations such as dermatitis, diarrhea, and dementia; therefore, we tested the hypothesis that patients with AIDS and diarrhea would have niacin depletion. This study compared 24-h urine excretion of N1-methyl-nicotinamide (N1MN) among patients with pellagra and patients with AIDS who did and did not have diarrhea. METHODS: Three groups were studied: G1 (patients with AIDS and diarrhea, n = 5); G2 (patients with AIDS and no diarrhea, n = 7), and G3 (patients with alcoholic pellagra and without the human immunodeficiency virus, n = 8). Diarrhea was defined as the production of at least three liquid stools per day over 3 to 5 d. Studies included mucosal intestinal biopsy, malabsorption tests, detection of parasites in stool, and serum albumin measurements. Semiquantitative food-frequency questionnaire, anthropometry, and daily urinary N1MN excretion were also determined. Groups were matched in relation to age, sex, presence of parasites in stool, and intestinal absorption results. RESULTS: G1 had normal intestinal examination by light microscopy and no parasites in stools. G2 group showed lower levels of serum albumin (2.6 +/- 0.3 g/dL) when compared with G1 (3.4 +/- 0.3 g/dL) and G3 (3.1 +/- 0.7 g/dL). Except for patients with pellagra, groups met their energy requirements. Patients in G3 (0.013, 0.01-0.081 mg/dL) and G1 (0.062, 0.001-0.33 mg/dL) excreted smaller amounts of N1MN in urine than did those in G2 (0.63, 0.02-2.9 mg/dL). CONCLUSIONS: Patients with AIDS and diarrhea excreted less N1MN in urine than did those without diarrhea. These patients may have an impaired niacin nutritional status, possibly associated with increased metabolic needs.

Pathologic findings in the adrenal glands of autopsied patients with acquired immunodeficiency syndrome.

A morphologic evaluation was carried out on adrenal glands from 128 autopsied patients with the acquired immunodeficiency syndrome (AIDS). The adrenal gland was compromised in 99.2% of the cases, with distinct pathological features and infectious agents. Inflammatory infiltrates were observed in 99.2% of the cases with a predominance of mononuclear cells in 97.4%, affecting mainly the medulla. Necrosis, fibrosis, hemorrhages and neoplasias were observed. We also described 3 (2.3%) cases of calcification located in the adrenal gland central vein (AGCV). This is seldom mentioned in the literature. Cytomegalovirus was the most frequent infectious agent, observed in 48.4% of cases. Balamuthia mandrillaris, a free living ameba, was found in one case affecting the entire gland. We also found a nest of Trypanosoma cruzi in the musculature of the AGCV. The presence of the nest of T cruzi in AGCV may play a role in the reactivation of this infection in immunosuppressed individuals. Pathologic processes and opportunistic infections may contribute to the alterations in the adrenal gland that lead to multiple organ failure observed in terminal AIDS patients.

Th1/Th2 immune responses are associated with active cutaneous leishmaniasis and clinical cure is associated with strong interferon-gamma production.

In leishmaniasis, Th1-related cytokines production seems to be crucial for host control of parasite burden and clinical cure. Visceral and diffuse cutaneous leishmaniasis are characterized by negative skin test for parasite antigens and failure to produce Th1 cytokines, whereas tegumentary leishmaniasis is characterized by positive skin test and the ability of peripheral blood mononuclear cells (PBMCs) to produce Th1 cytokines. In this study, specific antibody plasma levels and cytokine production in PBMC culture supernatants were evaluated by enzyme-linked immunoabsorbent assay in patients with active or cured cutaneous leishmanial lesions and in subjects without disease history living in the same endemic area. Higher tumor necrosis factor-alpha, interferon (IFN)-gamma, interleukin (IL)-12, IL-4, and IL-10 levels were observed in patients with active lesions, whereas cured subjects produced only IFN-gamma at elevated levels. Analysis of specific antibody isotypes correlate with cellular immune response observed in vitro, as the production of IgG1 and IgG3 was higher in patients with active lesions. Our results suggest the presence of a mixed Th1/Th2 response during active disease and that clinical cure is associated with a sustained Th1 response characterized by elevated IFN-gamma levels and down-modulation of IL-4 and IL-10 production.