Inflammatory mediators from monocytes down-regulate cellular proliferation and enhance cytokines production in patients with polar clinical forms of Chagas disease

Exposure to Trypanosoma cruzi parasites induces monocytes and macrophages to produce various endogenous mediators, including prostaglandins and cytokines. To clarify the involvement of monocytes as an important source of inflammatory mediators in Chagas disease patients, we evaluated PBMC before and after depletion of adherent cells (monocytes) from patients with indeterminate (IND) and cardiac (CARD) clinical forms and from non-infected individuals (NI). We demonstrated that after the partial depletion of adherent cells, production of PGE2 was slightly decreased in patients with Chagas disease. Inhibition of the cells by indomethacin increased the proliferation in PBMC cells from patients after antigen stimulation. Pro-inflammatory cytokines as IL-2 and IFN-γ also had a greater decrease after partial depletion of adherent cells in both clinical forms of Chagas disease. IL-10 and IL-5 levels were also reduced after partial depletion of adherent cells both in IND and CARD patients. In addition, we evaluated the APC potential of B cells and observed that the MHCII and CD80 molecules had an increased expression after partial depletion of most monocytes in all groups. Thus, inflammatory mediators produced by monocytes seem to be important to modulate immune responses in Chagas disease by regulating the processes of inflammation and antigen presentation.     

Human Infection with Shewanella putrefaciens and S. algae: Report of 16 Cases in Martinique and Review of the Literature

Shewanella spp. are saprophytic bacteria that are part of the marine microflora in warm climates and are rarely pathogenic. However, Shewanella spp. infections are being increasingly reported, and there has been no comprehensive review of the literature describing these infections. This article reports 16 cases of Shewanella spp. infections in Martinique since 1997 and reviews another 239 cases reported in the literature since 1973. Patients experienced soft tissue infections, ear infection, or abdominal and biliary tract infections. A skin or mucosal portal of entry was found for 53% of the patients and exposure to the marine environment was reported for 44%; 79% of patients had an underlying condition. Bacteriema were frequent (28%). Most (87%) patients recovered, although ear infections can become chronic. Death occurred in 13% of the patients. Most Shewanella spp. isolates are susceptible to cefotaxime (95%), piperacillin and tazobactam (98%), gentamicin (99%), and ciprofloxacin (94%).     

Syndrome in Question

Hay-Wells syndrome or AEC (Ankyloblepharon, Ectodermal dysplasia and Cleft lip and palate syndrome) is a rare ectodermal disorder. The treatment is aimed to prevent clinical complications. We describe the case of a four-month old male patient with erosions on the scalp, trunk and arms, trachyonychia, deformity of the ears, micropenis, cleft palate, decreased eyebrow and eyelash hairs, in addition to antecedents of surgical correction of ankyloblepharon. The importance of the correct diagnosis is emphasized, besides the investigation of the associated diseases, treatment of complications and genetic counseling of the parents.     

Factors Associated with Severe Leptospirosis,Martinique, 2010–2013

To identify factors associated with disease severity, we examined 102 patients with quantitative PCR–confirmed leptospirosis in Martinique during 2010–2013. Associated factors were hypotension, chest auscultation abnormalities, icterus, oligo/anuria, thrombocytopenia, prothrombin time <68%, high levels of leptospiremia, and infection with L. interrogans serovar Icterohaemorrhagiae/Copenhageni.     

A novel CRYAB mutation resulting in multisystemic disease

Mutations in the CRYAB gene, encoding alpha-B crystallin, cause distinct clinical phenotypes including isolated posterior polar cataract, myofibrillar myopathy, cardiomyopathy, or a multisystemic disorder combining all these features. Genotype/phenotype correlations are still unclear. To date, multisystemic involvement has been reported only in kindred harboring the R120G substitution. We report a novel CRYAB mutation, D109H, associated with posterior polar cataract, myofibrillar myopathy and cardiomyopathy in a two-generation family with five affected individuals. Age of onset, clinical presentation, and muscle abnormalities were very similar to those described in the R120G family. Alpha-B crystallin may form dimers and acts as a chaperone for a number of proteins. It has been suggested that the phenotypic diversity could be related to the various interactions between target proteins of individual mutant residues. Molecular modeling indicates that residues D109 and R120 interact with each other during dimerization of alpha-B crystallin; interestingly, the two substitutions affecting these residues (D109H and R120G) are associated with the same clinical phenotype, thus suggesting a similar pathogenic mechanism. We propose that impairment of alpha-B crystallin dimerization may also be relevant to the pathogenesis of these disorders.     

Matrix Metalloproteinases 2 and 9 Are Differentially Expressed in Patients with Indeterminate and Cardiac Clinical Forms of Chagas Disease

Dilated chronic cardiomyopathy (DCC) from Chagas disease is associated with myocardial remodeling and interstitial fibrosis, resulting in extracellular matrix (ECM) changes. In this study, we characterized for the first time the serum matrix metalloproteinase 2 (MMP-2) and MMP-9 levels, as well as their main cell sources in peripheral blood mononuclear cells from patients presenting with the indeterminate (IND) or cardiac (CARD) clinical form of Chagas disease. Our results showed that serum levels of MMP-9 are associated with the severity of Chagas disease. The analysis of MMP production by T lymphocytes showed that CD8⁺ T cells are the main mononuclear leukocyte source of both MMP-2 and MMP-9 molecules. Using a new 3-dimensional model of fibrosis, we observed that sera from patients with Chagas disease induced an increase in the extracellular matrix components in cardiac spheroids. Furthermore, MMP-2 and MMP-9 showed different correlations with matrix proteins and inflammatory cytokines in patients with Chagas disease. Our results suggest that MMP-2 and MMP-9 show distinct activities in Chagas disease pathogenesis. While MMP-9 seems to be involved in the inflammation and cardiac remodeling of Chagas disease, MMP-2 does not correlate with inflammatory molecules.