Characterization of immune responses during infection with Mycobacterium avium strains 100, 101 and the recently sequenced 104

Abstract

Summary Mycobacterium avium strain 104 was chosen as the M. avium isolate to sequence, as it is virulent to humans, stable and readily transfectable. As this strain has not been widely studied we sought to investigate the pattern of 104 infection in mice. Bacterial growth and the immune response generated were compared with infection with the low virulence M. avium strain 100, and the high virulence common laboratory strain, 101. Mycobacterium avium strains 104 and 101 grew progressively within mice, while strain 100 was gradually cleared. Strains 104 and 101 induced strong T cell activation and spleen cell cultures produced similar levels of IFN-γ . In mice infected with strain 100 no significant T cell activation or IFN-γ production was measured. Further, mice infected with strain 104 or 101 also displayed comparable inflammatory responses and similar granuloma formation, while only minimal inflammation was seen in mice infected with strain 100. Strains 101 and 104 also grew in a similar fashion in bonemarrow-derived macrophages and induced significant levels of TNF and nitric oxide. Thus infection with M. avium strain 104 induced an immunological response comparable to M. avium strain 101 and, with the availability of its sequence, should be a useful tool for designing new vaccines or drugs therapies to treat the increasing incidence of M. avium infection in humans.

Quiescent haematopoietic stem cells are activated by IFN-γ in response to chronic infection

“…3). These changes are consistent with mobilization of a T-cell-mediated immune response, characteristic of ongoing mycobacterial disease15.…”

“…1)15. Despite infection with M. avium , the absolute numbers of lymphocytes, neutrophils, monocytes, eosinophils and basophils in peripheral blood remained stable; the only significant changes in blood composition were a decrease in platelet number at 2 weeks postinfection (Supplementary Fig.…”

“…Because IFNγ is strongly upregulated during M. avium infection15, 22, we focused our attention on the interferons23. We hypothesized that IFNγ is responsible for the proliferative response of HSCs during M. avium infection.…”

Potent Antimycobacterial Activity of the Pyridoxal Isonicotinoyl Hydrazone Analog 2-Pyridylcarboxaldehyde Isonicotinoyl Hydrazone: A Lipophilic Transport Vehicle for Isonicotinic Acid Hydrazide

“…Cultures were incubated on rollers at 37°C in a dry incubator. To generate luminescent M. bovis BCG and M. avium strain 104 (Saunders et al, 2002), bacteria were rendered electrocompetent by standard methods (Lee et al, 2002) and transformed with 2 ml of pSMT1 (Snewin et al, 1999) by electroporation (25 mF, 2.5 kV, 200 V). Transformants were selected on Middlebrook 7H11 plates supplemented with 25 mg/ml hygromycin (Sigma-Aldrich).…”

Complete Genome Sequence of Mycobacterium avium subsp. hominissuis Strain H87 Isolated from an Indoor Water Sample

“…ANIs relative to the MAH H87 genome are 99.19% for M. avium 104, 98.74% for MAH TH135, 86.10% for M. intracellulare ATCC 13950, and 85.96% for M. chimaera AH16. Therefore, of the four genome comparisons, environmental strain H87 is most closely related to M. avium 104 [a strain isolated from an AIDS patient that is known to cause lung infections in a murine model (9, 10)] and MAH TH135 [a strain isolated from an HIV-negative patient with pulmonary MAC disease (11)].…”