Unusual Differences in the Pulmonary Histopathology of Mice after Intranasal Infection with Mycelial Propagules of Histoplasma capsulatum Strains Classified as LAm A2 and NAm 2 Phylogenetic Species.

The ascomycete Histoplasma capsulatum is the causative agent of systemic respiratory mycosis histoplasmosis, which sometimes develops acute disseminated or chronic clinical forms, with the latter usually associated with granuloma formation. The present report shows differential histopathological changes in the pulmonary inflammatory response of mice infected intranasally with the mycelial morphotype of H. capsulatum strains with distinct genotypes, EH-46 and G-217B, classified as LAm A2 and NAm 2 phylogenetic species, respectively. Infected male BALB/c mice were sacrificed at different postinfection times, and their serial lung sections were stained with periodic acid-Schiff and analyzed via microscopy. In mice infected with the LAm A2 strain, the results showed progressive changes in the inflammatory infiltrate of the lung parenchyma during the first hours and days postinfection as well as granulomas with macrophages containing intracellular yeast cells, which prevailed at 14 and 21 days postinfection. Bronchiolar-associated lymphoid tissue was induced in mice infected with both strains, primarily in mice infected with the NAm 2 strain. Several lung sections from mice infected with the LAm A2 strain showed PAS-positive yeast cells aggregated in a perinuclear crown-like arrangement in macrophages from 3 h to 21 days postinfection. These findings highlight differences in the host pulmonary inflammatory response associated with distinct H. capsulatum species.

Exposure to Sub-Lethal Doses of Permethrin Is Associated with Neurotoxicity: Changes in Bioenergetics, Redox Markers, Neuroinflammation and Morphology.

Permethrin (PERM) is a member of the class I family of synthetic pyrethroids. Human use has shown that it affects different systems, with wide health dysfunctions. Our aim was to determine bioenergetics, neuroinflammation and morphology changes, as redox markers after subacute exposure to PERM in rats. We used MDA determination, protein carbonyl assay, mitochondrial O2 consumption, expression of pro-inflammatory cytokines and a deep histopathological analysis of the hippocampus. PERM (150 mg/kg and 300 mg/kg body weight/day, o.v.) increased lipoperoxidation and carbonylated proteins in a dose-dependent manner in the brain regions. The activities of antioxidant enzymes glutathione peroxidase, reductase, S-transferase, catalase, and superoxide dismutase showed an increase in all the different brain areas, with dose-dependent effects in the cerebellum. Cytokine profiles (IL-1ß, IL-6 and TNF-α) increased in a dose-dependent manner in different brain tissues. Exposure to 150 mg/kg of permethrin induced degenerated and/or dead neurons in the rat hippocampus and induced mitochondrial uncoupling and reduction of oxidative phosphorylation and significantly decreased the respiratory parameters state 3-associated respiration in complex I and II. PERM exposure at low doses induces reactive oxygen species production and imbalance in the enzymatic antioxidant system, increases gene expression of pro-inflammatory interleukins, and could lead to cell damage mediated by mitochondrial functional impairment.

Effect of coinfection with influenza virus and bacteria on host damage.

BACKGROUND: Influenza virus infection is often complicated by a bacterial infection, with this coinfection causing severe pneumonia. If not timely treated, the disease can cause death. OBJECTIVE: To demonstrate, in animal models, that coinfection with influenza virus and bacteria that affect the respiratory tract causes multisystemic damage. METHOD: Six groups of mice were formed: a control group, one infected with the influenza virus, two infected with bacteria: Haemophilus influenzae and Streptococcus pneumoniae, respectively; and two co-infected with influenza virus and Haemophilus influenzae or Streptococcus pneumoniae, respectively. RESULTS: Of the six groups of mice, only the group co-infected with influenza virus and Streptococcus pneumoniae showed damage to thoracic and abdominal organs. A decrease in serum cytokine levels was found in all study groups, which was more pronounced in the co-infected mice. CONCLUSIONS: The groups of mice infected with Streptococcus pneumoniae or influenza virus alone showed no damage, which indicates that coexistence of these infections caused the damage in the group of co-infected mice.

ANTECEDENTES: La infección por el virus de la influenza con frecuencia se complica con una infección bacteriana, coinfección que provoca cuadros graves de neumonía, la cual puede ocasionar la muerte si no es tratada en forma oportuna. OBJETIVO: Demostrar en modelos animales que la coinfección por el virus de la influenza y bacterias que afectan el tracto respiratorio ocasiona daño multisistémico. MÉTODO: Se formaron seis grupos de ratones: un grupo control, uno infectado de virus de la influenza, dos infectados de bacterias: Haemophilus influenzae y Streptococcus pneumoniae, respectivamente; y dos coinfectados de virus de la influenza y Haemophilus influenzae y Streptococcus pneumoniae, respectivamente. RESULTADOS: De los seis grupos de ratones, solo en el grupo coinfectado de virus de la influenza y Streptococcus pneumoniae se observó daño en órganos torácicos y abdominales. En todos los grupos se encontró disminución de los niveles séricos de las citocinas, mayor en los ratones coinfectados. CONCLUSIONES: Los grupos de ratones infectados solo de Streptococcus pneumoniae o el virus de la influenza no presentaron daños, lo cual indica que la coexistencia de estas infecciones fue la que ocasionó el daño en el grupo de ratones coinfectados.

Effect of coinfection with influenza virus and bacteria on host damage / Efecto de la coinfección por virus de la influenza y bacterias en el daño al hospedero

Abstract Background: Influenza virus infection is often complicated by a bacterial infection, with this coinfection causing severe pneumonia. If not timely treated, the disease can cause death. Objective: To demonstrate, in animal models, that coinfection with influenza virus and bacteria that affect the respiratory tract causes multisystemic damage. Method: Six groups of mice were formed: a control group, one infected with the influenza virus, two infected with bacteria: Haemophilus influenzae and Streptococcus pneumoniae, respectively; and two co-infected with influenza virus and Haemophilus influenzae or Streptococcus pneumoniae, respectively. Results: Of the six groups of mice, only the group co-infected with influenza virus and Streptococcus pneumoniae showed damage to thoracic and abdominal organs. A decrease in serum cytokine levels was found in all study groups, which was more pronounced in the co-infected mice. Conclusions: The groups of mice infected with Streptococcus pneumoniae or influenza virus alone showed no damage, which indicates that coexistence of these infections caused the damage in the group of co-infected mice.

Resumen Antecedentes: La infección por el virus de la influenza con frecuencia se complica con una infección bacteriana, coinfección que provoca cuadros graves de neumonía, la cual puede ocasionar la muerte si no es tratada en forma oportuna. Objetivo: Demostrar en modelos animales que la coinfección por el virus de la influenza y bacterias que afectan el tracto respiratorio ocasiona daño multisistémico. Método: Se formaron seis grupos de ratones: un grupo control, uno infectado de virus de la influenza, dos infectados de bacterias: Haemophilus influenzae y Streptococcus pneumoniae, respectivamente; y dos coinfectados de virus de la influenza y Haemophilus influenzae y Streptococcus pneumoniae, respectivamente. Resultados: De los seis grupos de ratones, solo en el grupo coinfectado de virus de la influenza y Streptococcus pneumoniae se observó daño en órganos torácicos y abdominales. En todos los grupos se encontró disminución de los niveles séricos de las citocinas, mayor en los ratones coinfectados. Conclusiones: Los grupos de ratones infectados solo de Streptococcus pneumoniae o el virus de la influenza no presentaron daños, lo cual indica que la coexistencia de estas infecciones fue la que ocasionó el daño en el grupo de ratones coinfectados.

Immune Response Induced by an Immunodominant 60 kDa Glycoprotein of the Cell Wall of Sporothrix schenckii in Two Mice Strains with Experimental Sporotrichosis.

Cell wall (CW) components of fungus Sporothrix schenckii are the major inductors antigens of immune responses. The immunodominant 60 kDa glycoprotein (gp60) has been shown to be associated with the virulence of this fungus but its role in experimental sporotrichosis is unknown. In this work, the immunological effects of CW-purified gp60 were investigated in a model of experimental subcutaneous sporotrichosis in normal and gp60-preimmunized C57BL/6 and BALB/c mice strains which were then infected with S. schenckii conidia. Results showed that both mice strains use different cytokine profiles in order to fight S. schenckii infection; C57BL/6 mice seem to use a Th17 response while BALB/c mice tend to depend on a Th1 profile. Preimmunization with gp60 showed a downregulatory effect on the immune response since cytokines levels were diminished in both strains. There were no significant differences in the magnitude of dorsoplantar inflammation between gp60-preimmunized and nonimmunized mice of both strains. However, skin lesions due to the infection in gp60-preimmunized mice were more severe in BALB/c than in C57BL/6 mice, suggesting that the antigen exerts a higher downregulatory effect on the Th1 response.

Hematological Effects, Serum, and Pulmonary Cytokine Profiles in a Melanoma Mouse Model Treated with GK1.

OBJECTIVE: In a previous study, we demonstrated the therapeutic efficacy of a subcutaneous injection of GK1 peptide in a melanoma mouse model, effectively increasing the mean survival time by 42.58%, delaying tumor growth, and increasing intratumoral necrosis compared with the control. As a first approach to investigate the anti-melanoma effect of GK1, this study was carried out to determine the hematological effects along with both serum and lung cytokine profiles in a melanoma lung metastatic model. MATERIALS AND METHODS: Thirteen C57BL6 female mice were transfected in the lateral tail vein with 2×10(5) B16-F0 melanoma cells. After 7 days, mice were separated in two different groups and treatments were initiated (day 0): The GK1-treated group (seven mice) were injected every 5 days intravenously with GK1 (10 µg) in the lateral tail vein, and the control group (six mice) were injected every 5 days with intravenous saline solution. Blood samples were collected every 5 days from day 0; tumor samples were obtained for cytokine measurements on the day of sacrifice. RESULTS: In the peripheral blood, mice treated with GK1 presented a statistically significant decrease in IFN-γ (p<0.05), and lymphocytes tended to be lower compared with the control mice (p=0.06). Lung metastatic analysis demonstrated a significant increase in IFN-γ and IL-12p70 (p<0.05); a significant decrease in IL-17, IL-4, IL-22, IL-23, and IL-12p40 (p<0.05); and a marginal decrease in IL-1ß (p=0.07) compared with the control. DISCUSSION: Our results suggest that an intratumoral increase of cytokines with antitumor activity along with an intratumoral decrease of cytokines with protumor activity could explain, in part, the anti-melanoma effects of GK1 in a lung metastatic melanoma mouse model. Further studies must be performed to elucidate the precise mechanisms of action for GK1 peptide against melanoma, and their eventual application in humans.

Retrospective serological survey of influenza viruses in backyard pigs from Mexico City.

BACKGROUND: In the present study, we analyzed the presence of antibodies to four different influenza viruses (pH1N1, hH1N1, swH1N1, and swH3N2) in the sera of 2094 backyard pigs from Mexico City. The sera were obtained between 2000 and 2009. OBJECTIVES: The aim of this study was to perform a retrospective analysis of the 2000-2009 period to determine the seroprevalence of antibodies against pH1N1, hH1N1, swH1N1, and swH3N2 viruses in sera obtained from backyard pigs in Mexico City. METHODS: Antibody detection was conducted with hemagglutination inhibition assay (HI) using four influenza viruses. We used linear regression to analyze the tendency of antibody serum titers throughout the aforementioned span. RESULTS: We observed that the antibody titers for the pH1N1, swH1N1, and swH3N2 viruses tended to diminish over the study period, whereas the antibodies to hH1N1 remained at low prevalence for the duration of the years analyzed in this study. A non-significant correlation (P > 0.05) between antibody titers for pH1N1 and swH1N1 viruses was observed (0.04). It contrasts with the significance of the correlation (0.43) observed between the swH1N1 and swH3N2 viruses (P < 0.01). CONCLUSIONS: Our findings showed no cross-antigenicity in the antibody response against the same subtype. Antibodies against pH1N1 virus were observed throughout the 10-year study span, implying that annual strains shared some common features with the pH1N1 virus since 2000, which would then be capable of supporting the ongoing presence of these antibodies.