The relative importance of T cell subsets in immunity and immunopathology of airborne Mycobacterium tuberculosis infection in mice.

Wild-type (WT) and targeted-mutant mice incapable of making alphabeta T cells, gammadelta T cells, class I major histocompatibility complex (MHC), class II MHC, interferon (IFN)-gamma, or inducible nitric oxide synthase (NOS2), were infected with Mycobacterium tuberculosis (Mtb) by aerosol, and monitored over time for their ability to (a) control infection, (b) develop histopathology at sites of infection, and (c) survive. WT mice acquired the ability to control and to hold infection at a stationary level from day 20 on. This was associated with the development of a macrophage-dominated alveolitis at sites of infection, with increased synthesis of IFN-gamma and NOS2 mRNA, and with an median survival time (MST) of 258.5 d. In the absence of alphabeta T cells, Mtb grew progressively and rapidly to induce a necrotic, neutrophil-dominated lung pathology that killed mice with an MST of 48 d. In the absence of CD4-mediated immunity (class II(-/-) mice), progressive bacterial growth continued in the lungs and in other organs beyond day 20, resulting in an MST of 77 d. By contrast, in the absence of CD8 T cell-mediated immunity, lung infection was controlled at a 1 log higher stationary level that induced a similar histopathologic response to that of WT mice, and resulted in an MST of 232 d.

Growth rate of mycobacteria in mice as an unreliable indicator of mycobacterial virulence.

The CDC1551 strain of Mycobacterium tuberculosis was compared with the H37Rv strain of M. tuberculosis and the Ravenel strain of Mycobacterium bovis for virulence in mice. Although all three strains gave rise to the same level of stationary infection in major organs, mice infected with the Ravenel strain died much earlier from lung disease.

Characterization of two mannose-binding protein cDNAs from rhesus monkey (Macaca mulatta): structure and evolutionary implications.

Mannose-binding proteins (MBPs), members of the collectin family, have been implicated as lectin opsonins for various viruses and bacteria. Two distinct but related MBPs, MBP-A and MBP-C, with approximately 55% identity at the amino acid level, have been previously characterized from rodents. In humans, however, only one form of MBP has been characterized. In this paper we report studies elucidating the evolution of primate MBPs. ELISA and Western blot analyses indicated that rhesus and cynomolgus monkeys have two forms of MBP in their sera, while chimpanzees have only one form, similar to humans. Two distinct MBP cDNA clones were isolated and characterized from a rhesus monkey liver cDNA library. Rhesus MBP-A is closely related to the mouse and rat MBP-A, showing 77% and 75% identity at the amino acid level, respectively. Rhesus MBP-A also has three cysteines at the N-terminus, similar to mouse and rat MBP-A and human MBP. Rhesus MBP-C shares 90% identity with the human MBP at the amino acid level and has three cysteines at the N-terminus, in contrast to two cysteine residues found in rodent MBP-C. A stretch of nine amino acids close to the N-terminus, absent in both mouse and rat MBP-A, but present in rodent MBP-C, chicken and human MBPs, is also found in the rhesus MBP-A. The phylogenetic analysis of rhesus and other mammalian MBPs, coupled with the serological data suggest that at least two distinct MBP genes existed prior to mammalian radiation and the hominoid ancestor apparently lost one of these genes or failed to express it.