Alma Y. Arce-Mendoza

Expression of CD64, CD206, and RAGE in Adherent Cells of Diabetic Patients Infected with Mycobacterium tuberculosis

BACKGROUND CD64 and CD206 receptors play an important role in the internalization of Mycobacterium tuberculosis into macrophages. RAGE, described in diabetes (a predisposing factor for tuberculosis), captures glycosylated proteins. METHODS Four groups of 15 patients with type 2 diabetes mellitus (DM2), pulmonary tuberculosis (PTB), type 2 diabetes and pulmonary tuberculosis (DM2-PTB), and controls (CG) were studied. Blood was obtained and mononuclear cells (MNC) isolated and cultured to obtain adherent cells (AC) and then stimulated with M. tuberculosis H37Rv lipids. Expression of CD64, CD206 and RAGE was measured by flow cytometry. RESULTS In the groups without stimulus, PTB and DM2-PTB expressed greater mean fluorescence intensity (MFI) of CD64 and CD206 compared to CG. DM2-PTB showed a decrease in expression compared to PTB. After lipid stimulation no significant difference between groups occurred. In AC without stimulus, RAGE expression was significantly greater in DM2, PTB and DM2-PTB. When DM2-PTB was compared to PTB, a significant decrease in expression occurred. After lipid stimulation, only DM2 cells showed greater MFI. CONCLUSIONS Diabetes affects expression of the three receptors. PTB cells significantly increase them. Diabetes and tuberculosis infection decrease expression compared to PTB alone. Diabetes did not alter CD64 and CD206 expression in infected patients. RAGE expression increases in patients with PTB as well as in diabetics. This suggests that RAGE could also behave as a receptor for M. tuberculosis.

Expression of CDllc in Blood Monocytes as Biomarker for Favorable Response to Antituberculosis Treatment

CD11c is involved in Mycobacterium tuberculosis phagocytosis by human macrophages. CD11c has not been evaluated during antituberculosis (anti-TB) treatment. CD11c expression was evaluated on monocytes from peripheral blood leukocytes of pulmonary TB (PTB) patients and healthy controls by flow cytometry, whereas CD11c/Arg47Trp polymorphism was analyzed using polymerase chain reaction-restriction fragment length polymorphism. PTB patients had increased levels of CD11c on blood monocytes as compared to healthy controls. CD11c levels decreased in response to anti-TB treatment. CD11c/Arg47Trp polymorphism is not associated with PTB.

Possible association of rare polymorphism in the ABCB1 gene with rifampin and ethambutol drug-resistant tuberculosis

Human P-glycoprotein (P-gp) is a membrane transporter encoded by ABCB1 (also known as MDR1) that plays a critical role in pharmacokinetics of many unrelated drugs. Rifampin (RMP) and ethambutol (ETB), two anti-tubercular agents, are substrates of P-gp. Single nucleotide polymorphisms (SNPs) in ABCB1 have been associated with resistance to several drugs; however, their association with RMP and ETB resistance in tuberculosis patients has not yet been studied. Genotype/allele frequencies in C1236T, G2677T/A and C3435T SNPs of ABCB1 were obtained from 99 tuberculosis patients susceptible or resistant to RMP and ETB (NoRER or RER). 2677G>A allele prevalence was found to be significantly higher in the RER group compared to NoRER (5 resistant vs 2 non-resistant patients, P < 0.01; OR, 11.0; 95% CI, 2.00-56.00). No differences were found in genotype/allele frequencies in C1236T and C3435T SNPs of ABCB1 and resistance to RMP and ETB in tuberculosis patients (P > 0.05). The present study suggests the 2677G>A allele of ABCB1 could be associated with simultaneous resistance to RMP and ETB in pulmonary tuberculosis patients. Further studies with larger sample sizes are needed to confirm this association and explore its nature.

Murine interferon-gamma inducible protein-10 (IP-10) secreted by Lactococcus lactis chemo-attracts human CD3+ lymphocytes

Chemokines are members of the super family of cytokines necessary for leukocyte recruitment in tissues and lymphoid organs. The interferon-gamma inducible protein-10 (IP-10) chemo-attracts CXCR3-expressing cells, such as activated T lymphocytes and monocytes. We have genetically engineered a strain of Lactococcus lactis to secrete a biologically active murine IP-10 that interacts with human CXCR3, its homolog receptor, and chemo-attracts human CD3+ T lymphocytes.

Interferon γ and interleukin 10 responses in immunocompetent and immunosuppressed New Zealand White rabbits naturally infected with Encephalitozoon cuniculi

Levels of interferon (IFN)-γ and interleukin (IL)-10 were measured in the serum of immunocompetent and immunosuppressed New Zealand White rabbits naturally infected with Encephalitozoon cuniculi. IFN-γ levels were elevated in infected rabbits, and a synergic effect was observed in animals treated with the immunosuppressive agent dexamethasone (Dex). The role of IL-10 in infected rabbits remains unclear, as IL-10 levels were similar to those of negative controls. Dex appeared to exhibit a proinflammatory effect, as IFN-γ levels were elevated in infected immunosuppressed rabbits. Similarly, Dex exhibited a synergic effect in infected immunosuppressed rabbits, as evidenced by the elevation in IFN-γ production. These data indicate that the immune response to this glucocorticoid should be considered in the design of future animal model studies of immunosuppression.

Inflammatory and Anti-inflammatory Responses Co-exist Inside Lung Granuloma of Fatal Cases of Coccidioidomycosis: A Pilot Report

Coccidioidomycosis is a fungal disease caused by Coccidioides immitis or Coccidioides posadasii. These fungi are endemic in the southern USA and northern Mexico. Immunocompromised patients are susceptible to develop severe forms of this fungal infection. Cytokines play an important role in controlling the fungal infection, but little is known about the predominant immunological environment in human lung tissue from fatal cases. Our aim was to analyze the pro-inflammatory and anti-inflammatory cytokines and monocyte/macrophages markers (CD14 and CD206) in the granulomas of six fatal cases of coccidioidomycosis. Cytokines and surface markers were higher in coccidioidomycosis cases when compared to control (P < 0.05). CD14 positive cells were increased inside the coccidioidal granuloma when compared to the outside (P < 0.05). No differences were found in the number of CD206+ cells inside the granuloma when compared to the outer population (P > 0.05). Interestingly, an analysis of stain intensity signals showed an increased signaling of CD14, CD206, IL-10 and TNFα inside the granuloma when compared to the outside (P < 0.05). iNOS and IL-12 gene expression were not detected in coccidioidomycosis cases, while IL-10, IL-6 and TGFβ gene expression were detected, but the differences when compared to healthy lungs were not significant (P > 0.05). TNFα gene expression was lower in coccidioidomycosis cases when compared to healthy lung (P = 0.05). In conclusion, pro- and anti-inflammatory responses co-exist inside of the granulomas of fatal cases of coccidioidomycosis and the absent of iNOS and IL-12 gene expression may be related with patient’s outcome.