Nitric oxide determines the development of actinomycetoma by Nocardia brasiliensis in eNOS knockout C57BL/6 mice.

Mycetoma is a chronic human infectious disease that produces severe deformation frequently in the lower extremities. Etiological agents include fungi (eumycetoma) and bacteria (actinomycetoma) that produce similar clinical and microscopic changes. The clinical appearance includes swelling, abscesses, ulcers, scars and sinuses that drain purulent material with microbe microcolonies. The pathogenesis of actinomycetoma has been studied mainly in rodents. Using this approach, it was found that Nocardia brasiliensis produces proteases that may play a role in tissue damage, as well as immunosuppressive molecules, such as brasilicardin A. Nitric oxide (NO) is a molecule with biological activities depending on its local concentration. Its effect on killing intracellular bacteria such as Mycobacterium tuberculosis has been known for decades. NO plays an important role in innate and adaptive immunity. It can promote or suppress some biological activities despite its short half-ife. NO is produced by three different nitric oxide synthases (NOS). We used the genetic blockade of eNOS in C57BL/6 mice to demonstrate the role of NO in actinomycetoma development. Inflammation and actinomycetoma were prevented in genetically modified mice infected with N. brasiliensis. T cell proliferation was increased in these rodents, and antibody production, IL-6 and IL-10 expression were similar and TNF-α was lower.

Cortisol and perceived stress are associated with cytokines levels in patients infected with influenza B virus.

Influenza B virus (IBV) causes respiratory infectious disease. Cytokines are important immune mediators during infectious diseases. Cortisol and stress have been related to respiratory infection susceptibility and cytokine regulation. Little is known about systemic cytokines, cortisol, and perceived stress in the early stages of IBV infection. We researched the systemic cytokines and cortisol, as well as the perceived stress and blood cell count in patients infected with IBV. The diagnosis was established using the Luminex xTAG RVP kit and confirmed with qRT-PCR for IBV viral load. The perceived stress was evaluated using the perceived stress scale (PSS-10). Twenty-five plasma cytokines were determined using multiplex immunoassay and cortisol by ELISA. The leukocyte differential count was measured with a standard laboratory protocol. Th1, Th17, and IL-10 cytokines were higher in IBV infected patients (P < 0.05). Leukocytes and neutrophil count negatively correlated with viral load (P < 0.05). Perceived stress had a negative effect on monocyte and systemic cytokines in IBV infected patients (P < 0.05). Cortisol was higher in patients infected with IBV and correlated positively with CCL20 (P < 0.05). Cortisol showed a positive effect on most of the systemic cytokines (P < 0.05). In conclusion, a cytokine pattern was found in IBV infected patients, as well as the possible role of leukocyte counts in the control of IBV. Our results suggest the importance of cortisol and perceived stress on systemic cytokines in patients infected with IBV, but more studies are needed to understand their role in cytokine production in respiratory infectious disease.

Nocardia brasiliensis Modulates IFN-gamma, IL-10, and IL-12 cytokine production by macrophages from BALB/c Mice.

Interferon-gamma (IFN-gamma) is a critical cytokine involved in control of different infections. Actinomycetoma is a chronic infectious disease mainly caused by the bacterium Nocardia brasiliensis, which destroys subcutaneous tissue, including bone. Currently, the mechanism of pathogenesis in N. brasiliensis infection is not known. Here, we demonstrate that N. brasiliensis induced an IFN-gamma response in serum after 24 h of infection, while, in infected tissue, positive cells to IFN-gamma appeared in 2 early peaks: the first was present only 3 h after infection, then transiently decreased; and the second peak appeared 12 h after infection and was independent of interleukin-10. Resident macrophages produced an immediate IFN-gamma response 1 h after in vitro infection, and spleen-positive cells began later. The phase of growth of N. brasiliensis affected cytokine production, and exposure of macrophages to Nocardia opsonized with either polyclonal anti-Nocardia antibodies or anti-P61 monoclonal antibody led to a suppression of cytokine production. Our report provides evidence that N. brasiliensis as an intracellular bacterium modulates macrophage cytokine production, which helps survival of the pathogen. Modulation of these cytokines may contribute to pathogenesis once this bacterium is inside the macrophage.