Comparison of T cell cytokines in resistant and susceptible mice infected with virulent Brucella abortus strain 2308

Abstract

C57BL/10 and BALB/c mice differ in their abilities to clear infections with the intracellular bacterium Brucella abortus strain 2308. We have previously reported that in vivo of IL-10 in the susceptible BALB/c mice results in significantly fewer bacteria in their spleens 1 week after infection with 5 x 10(3) colony forming units (CFU) of 2308. Here we extend those studies and report a similar effect when IL-4 is neutralized. In contrast, in the more resistant C57BL/10 mice infected with 5 x 10(3) CFU, neither neutralization of IL-4 significantly decreased the level of infection nor did it in either BALB/c or C57BL/10 mice infected with a 1000-fold higher dose of strain 2308. While splenocytes from the later mentioned groups of mice produced IL-10 in response to stimulation with brucella antigen, they also produced higher levels of interferon (IFN)-gamma than those from BALB/c mice with the low challenge dose of 5 x 10(3) CFU. Results of in vivo neutralization of IFN-gamma by monoclonal antibodies (MAb) reported here and elsewhere indicated that IFN-gamma is important for control; thus, we postulate that the higher levels of IFN-gamma override the detrimental effects of Th2 cytokines. In vitro studies also showed that macrophages from the more resistant C57BL/10 mice were less susceptible to the ability of IL-10 to decrease anti-brucella activities than were BALB/c macrophages. CD4+ T cells were principally responsible for the production of IL-10 in BALB/c but not C57BL/10 splenocyte populations. C57BL/10 splenocytes produced more IFN-gamma than those from BALB/c mice in response to stimulation with brucella antigens. These differences between BALB/c and C57BL/10 mice may contribute to the superior capacity of C57BL/10 mice to control infections with B. abortus strain 2308.

Humoral Immunity and CD4+ Th1 Cells Are Both Necessary for a Fully Protective Immune Response upon Secondary Infection with Brucella melitensis

“…To increase our understanding of this phenomenon, we performed in this study a detailed analysis of the protective state, including the humoral and cellular immune response induced by the injection of HK or live, fully virulent B. melitensis 16M in mice. In addition, as C57BL/6 and BALB/c mice have been reported to display different levels of resistance to Brucella infection (46,52,53) and are frequently used in Brucella vaccination studies (38), we performed our comparison in both strains of mice.…”

La polarisation des macrophages, le noeud gordien des infections bactériennes ?

“…La brucellose chronique est clairement associée à une polarisation M2 puisque la neutralisation de l'IL-10 et de l'IL-4 restaure un profil M1 et l'activité microbicide des macrophages [23]. Les macrophages M2 sont également associés aux infections mycobactériennes chroniques : c'est ainsi que des macrophages M2 sont présents dans les lésions ulcéreuses précoces de la maladie de Buruli [24,34].…”

Brucella infection and vaccine studies in feral and domestic swine

“…98 Blockage of the Th1 cytokine cascade did not shift the response of mice to a Th2 response as IL-4 production was not elevated in the mouse splenocyte. 97 Studies in BALB/c mice, which have a marked lag in the upregulation of the Th1 response after…”

“…37 Murine models of brucellosis suggest that the lack of an IL-4 response is advantageous in allowing maximal production of Th-1 cytokines 39 and in the clearance of Brucella abortus. 40,41 Humoral immune responses were also significantly higher in swine parenterally The studies reported within Chapter 3 examined an isolated feral swine herd on an island on the Atlantic coast of South Carolina. This herd had been previously documented to be enzootically infected with Brucella based on serological assessments.…”

“…1 This phagocytosis is mediated by complement or Fc receptors, and lectin and fribronectin receptors mediate uptake in nonprofessional phagocytic cells. 41 Internalization of Brucella also appears to be dependent on the brucellar two component system BvrS-BvR which encodes for a histidine kinase sensor and its regulator protein. 110 This system seems to regulate the expression of several outer membrane proteins.…”