Comparative protection of mice against virulent and attenuated strains of Brucella abortus by passive transfer of immune T cells or serum

Araya, Luis Nazario; Winter, A J

doi:10.1128/iai.58.1.254-256.1990

“…Resistance to infection is dependent upon interferon-Q (IFN-Q) [2^6] which activates macrophages for anti-brucella activity [7], largely by enhancing production of reactive oxygen intermediates [8]. It is known that both CD4 and CD8 T cells mediate resistance to infection during the ¢rst week [9^12] and that they are more important than antibodies [13]. Both subpopulations of T cells could potentially contribute to protection through production of IFN-Q.…”

Section: Introductionmentioning

confidence: 99%

Major histocompatibility complex class I and II expression on macrophages containing a virulent strain of Brucella abortus measured using green fluorescent protein-expressing brucellae and flow cytometry

Murphy¹

2002

FEMS Immunology and Medical Microbiology

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Immune responses appropriate for control of an intracellular pathogen are generated in mice infected with Brucella abortus, shown by the ability of T cells to adoptively transfer resistance to naive mice. The infection nevertheless persists for months. It was hypothesized that one factor in maintaining the infection despite the presence of immune T cells was suboptimal expression of major histocompatibility complex (MHC) molecules on macrophages containing brucellae. This would allow B. abortus to elude detection by the host's immune system. To test this, B. abortus organisms expressing green fluorescent protein (GFP-Brucella) were constructed and three-color flow cytometry used to evaluate MHC expression on macrophages following in vitro or in vivo infection. When infected in vitro, the levels of MHC class I and class II expression on J774 macrophages containing GFP-Brucella were the same or higher than on macrophages without GFP-Brucella in the same cultures. Similarly, the MHC expression was higher on GFP(+) peritoneal exudate cells following infection or phagocytosis of heat-killed GFP-Brucella than it was on uninfected peritoneal exudate cells. Following in vivo infection of mice the level of MHC class I and II expression on GFP(+) cells in their spleens (the main site of infection) also tended to be as high as or higher than that on the GFP-negative cells. The only in vivo GFP(+) cells that showed a decreased MHC expression was a population of splenic Mac1(+) cells recovered from interferon-gamma gene-disrupted mice at the time of their death due to an overwhelming number of bacteria per spleen. Overall, it was concluded that decreased MHC expression is not a general principle associated with brucella infection of macrophages and thus not likely to contribute to maintenance of the chronic infection.

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“…Resistance to infection is dependent upon interferon‐γ (IFN‐γ) [2–6] which activates macrophages for anti‐brucella activity [7], largely by enhancing production of reactive oxygen intermediates [8]. It is known that both CD4 and CD8 T cells mediate resistance to infection during the first week [9–12] and that they are more important than antibodies [13]. Both subpopulations of T cells could potentially contribute to protection through production of IFN‐γ.…”

Section: Introductionmentioning

confidence: 99%

Major histocompatibility complex class I and II expression on macrophages containing a virulent strain ofBrucella abortusmeasured using green fluorescent protein-expressing brucellae and flow cytometry

Murphy¹,

Robertson²,

Parent³

et al. 2002

FEMS Immunology &Amp; Medical Microbiology

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Immune responses appropriate for control of an intracellular pathogen are generated in mice infected with Brucella abortus, shown by the ability of T cells to adoptively transfer resistance to naive mice. The infection nevertheless persists for months. It was hypothesized that one factor in maintaining the infection despite the presence of immune T cells was suboptimal expression of major histocompatibility complex (MHC) molecules on macrophages containing brucellae. This would allow B. abortus to elude detection by the host's immune system. To test this, B. abortus organisms expressing green fluorescent protein (GFP-Brucella) were constructed and three-color flow cytometry used to evaluate MHC expression on macrophages following in vitro or in vivo infection. When infected in vitro, the levels of MHC class I and class II expression on J774 macrophages containing GFP-Brucella were the same or higher than on macrophages without GFP-Brucella in the same cultures. Similarly, the MHC expression was higher on GFP(+) peritoneal exudate cells following infection or phagocytosis of heat-killed GFP-Brucella than it was on uninfected peritoneal exudate cells. Following in vivo infection of mice the level of MHC class I and II expression on GFP(+) cells in their spleens (the main site of infection) also tended to be as high as or higher than that on the GFP-negative cells. The only in vivo GFP(+) cells that showed a decreased MHC expression was a population of splenic Mac1(+) cells recovered from interferon-gamma gene-disrupted mice at the time of their death due to an overwhelming number of bacteria per spleen. Overall, it was concluded that decreased MHC expression is not a general principle associated with brucella infection of macrophages and thus not likely to contribute to maintenance of the chronic infection.

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“…Host-immune defenses against intracellular pathogens rely on cell-mediated and antibody-mediated mechanisms [17]. Several studies indicate that antibodies against intracellular pathogens present at the time of infection may have an important role in host protection [18][19][20].…”

Section: Introductionmentioning

confidence: 99%

B‐Cell Epitopes in the Immunodominant p34 Antigen of Mycobacterium avium ssp. paratuberculosis Recognized by Antibodies from Infected Cattle

Ostrowski

¹

,

Mundo

²

,

Harris

³

et al. 2003

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Mycobacterium avium ssp. paratuberculosis (M. paratuberculosis) causes Johne's disease, a chronic and fatal enteritis in ruminants. In the last stage of the disease, antibody titres rise and levels of interferon-g decrease, suggesting that the hostimmune response is switching from a T helper 1 (Th1) to a Th2 profile. In infected cattle, the membrane protein p34 elicits the predominant humoral response against M. paratuberculosis. To map the B-cell epitopes of this antigen, affinity-purified bovine antibodies against the carboxy-terminal region of p34 were used to screen a 12-mer phage display library. Several phage clones carrying peptides resembling fragments of p34 were affinity selected. Based on the predicted amino acid sequence, peptides were chemically synthesized, which demonstrated reactivity with serum from naturally infected and p34-vaccinated cattle. Immunization of mice with these peptides elicited an anti-p34 antibody response. Two B-cell epitopes were identified and characterized. Based on the reactivity and the type of immune response elicited, epitope A was determined to be conformational, whereas epitope B was demonstrated to be sequential. Both epitopes were shown to be present in p34 proteins from M. avium ssp. avium or M. paratuberculosis but absent from M. intracellulare, the other member of the M. avium complex. Furthermore, both epitopes were mapped to regions of p34 that display high variability when compared to homologous proteins from other mycobacterial species of public and animal health importance. We hypothesize that these variable regions of p34 may play a role in the immunobiology of M. paratuberculosis infections.

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Comparative protection of mice against virulent and attenuated strains of Brucella abortus by passive transfer of immune T cells or serum

Cited by 92 publications

References 9 publications

Major histocompatibility complex class I and II expression on macrophages containing a virulent strain of Brucella abortus measured using green fluorescent protein-expressing brucellae and flow cytometry

Major histocompatibility complex class I and II expression on macrophages containing a virulent strain of Brucella abortus measured using green fluorescent protein-expressing brucellae and flow cytometry

Major histocompatibility complex class I and II expression on macrophages containing a virulent strain ofBrucella abortusmeasured using green fluorescent protein-expressing brucellae and flow cytometry

B‐Cell Epitopes in the Immunodominant p34 Antigen of Mycobacterium avium ssp. paratuberculosis Recognized by Antibodies from Infected Cattle

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