RESUMO
The mechanisms underlying the immunopathology of tuberculous meningitis (TBM), the most severe clinical form of extrapulmonary tuberculosis (TB), are not understood. It is currently believed that the spread of Mycobacterium tuberculosis (Mtb) from the lung is an early event that occurs before the establishment of adaptive immunity. Hence, several innate immune mechanisms may participate in the containment of Mtb infection and prevent extrapulmonary disease manifestations. Natural killer (NK) cells participate in defensive processes that distinguish latent TB infection (LTBI) from active pulmonary TB (PTB). However, their role in TBM is unknown. Here, we performed a cross-sectional analysis of circulating NK cellCID="C008" value="s" phenotype in a prospective cohort of TBM patients (n = 10) using flow cytometry. Also, we addressed the responses of memory-like NK cell subpopulations to the contact with Mtb antigens in vitro. Finally, we determined plasma levels of soluble NKG2D receptor ligands in our cohort of TBM patients by enzyme-linked immunosorbent assay (ELISA). Our comparative groups consisted of individuals with LTBI (n = 11) and PTB (n = 27) patients. We found that NK cells from TBM patients showed lower absolute frequencies, higher CD69 expression, and poor expansion of the CD45RO+ memory-like subpopulation upon Mtb exposure in vitro compared to LTBI individuals. In addition, a reduction in the frequency of CD56brightCD16- NK cells characterized TBM patients but not LTBI or PTB subjects. Our study expands on earlier reports about the role of NK cells in TBM showing a reduced frequency of cytokine-producing cells compared to LTBI and PTB.
Assuntos
Células Matadoras Naturais/imunologia , Tuberculose Latente/imunologia , Mycobacterium tuberculosis/imunologia , Tuberculose Meníngea/imunologia , Tuberculose Pulmonar/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Citocinas/metabolismo , Feminino , Humanos , Imunidade Inata , Imunofenotipagem , Células Matadoras Naturais/metabolismo , Tuberculose Latente/sangue , Tuberculose Latente/microbiologia , Masculino , México , Pessoa de Meia-Idade , Estudos Prospectivos , Tuberculose Meníngea/sangue , Tuberculose Meníngea/microbiologia , Tuberculose Pulmonar/sangue , Tuberculose Pulmonar/microbiologia , Adulto JovemRESUMO
Isoniazid and pyrazinamide are both well-known hepatotoxic drugs. When isoniazid is used, the hepatic lesion appears before than when pyrazinamide is used. This paper intends to relate a case of a 5-month-old patient who had lungs' and meningeal tuberculosis and who developed toxic hepatitis accomplished by hepatic failure while he was being treated with isoniazid, pyrazinamide and rifampicin. The clinic manifestations and the laboratory alterations were detected in the fifth day of treatment and the recovery was fast; and almost complete by the end of the first week, in which the use of isoniazid had been suspended. Although it was necessary to take the patient to the intensive care unit, he had a good recovery, without sequels.