scholarly journals Phase Variations of the Mycoplasma penetrans Main Surface Lipoprotein Increase Antigenic Diversity

1999 ◽  
Vol 67 (4) ◽  
pp. 1569-1578 ◽  
Author(s):  
Olivier Neyrolles ◽  
Isabelle Chambaud ◽  
Stéphane Ferris ◽  
Marie-Christine Prevost ◽  
Tsuguo Sasaki ◽  
...  

ABSTRACT Mycoplasma penetrans is a recently identified mycoplasma, isolated from urine samples collected from human immunodeficiency virus (HIV)-infected patients. Its presence is significantly associated with HIV infection. The major antigen recognized during natural and experimental infections is an abundant P35 lipoprotein which, upon extraction, segregates in the Triton X-114 detergent phase and is the basis of M. penetrans-specific serological assays. We report here that the P35 antigen undergoes spontaneous and reversible phase variation at high frequency, leading to heterogeneous populations of mycoplasmas, even when derived from a clonal lineage. This variation was found to be determined at the transcription level, and although this property is not unique among the members of the class Mollicutes, the mechanism by which it occurs in M. penetrans differs from those previously described for other Mycoplasma species. Indeed, the P35 phase variation was due neither to a p35 gene rearrangement nor to point mutations within the gene itself or its promoter. The P35 phase variation in the different variants obtained was concomitant with modifications in the pattern of other expressed lipoproteins, probably due to regulated expression of selected members of a gene family which was found to potentially encode similar lipoproteins. M. penetrans variants could be selected on the basis of their lack of colony immunoreactivity with a polyclonal antiserum against a Triton X-114 extract, strongly suggesting that the mechanisms involved in altering surface antigen expression might allow evasion of the humoral immune response of the infected host.

2009 ◽  
Vol 83 (21) ◽  
pp. 10941-10950 ◽  
Author(s):  
Avi-Hai Hovav ◽  
Michael Santosuosso ◽  
Maytal Bivas-Benita ◽  
Andre Plair ◽  
Alex Cheng ◽  
...  

ABSTRACT In order to increase the immune breadth of human immunodeficiency virus (HIV) vaccines, strategies such as immunization with several HIV antigens or centralized immunogens have been examined. HIV-1 gp120 protein is a major immunogen of HIV and has been routinely considered for inclusion in both present and future AIDS vaccines. However, recent studies proposed that gp120 interferes with the generation of immune response to codelivered antigens. Here, we investigate whether coimmunization with plasmid-encoded gp120 alters the immune response to other coadministered plasmid encoded antigens such as luciferase or ovalbumin in a mouse model. We found that the presence of gp120 leads to a significant reduction in the expression level of the codelivered antigen in vivo. Antigen presentation by antigen-presenting cells was also reduced and resulted in the induction of weak antigen-specific cellular and humoral immune responses. Importantly, gp120-mediated immune interference was observed after administration of the plasmids at the same or at distinct locations. To characterize the region in gp120 mediating these effects, we used plasmid constructs encoding gp120 that lacks the V1V2 loops (ΔV1V2) or the V3 loop (ΔV3). After immunization, the ΔV1V2, but not the ΔV3 construct, was able to reduce antigen expression, antigen presentation, and subsequently the immunogenicity of the codelivered antigen. The V3 loop dependence of this phenomenon seems to be limited to V3 loops known to interact with the CXCR4 molecule but not with CCR5. Our study presents a novel mechanism by which HIV-1 gp120 interferes with the immune response against coadministered antigen in a polyvalent vaccine preparation.


Thorax ◽  
2001 ◽  
Vol 56 (6) ◽  
pp. 450-455
Author(s):  
E Mund ◽  
B Christensson ◽  
K Larsson ◽  
R Grönneberg

BACKGROUNDAge related changes in the immune system have been studied frequently but a possible relation to sex has not, to our knowledge, previously been examined. The effect of age and sex on the composition of lymphocyte subsets in bronchoalveolar lavage (BAL) fluid and peripheral blood was therefore examined.METHODSBronchoscopy with lavage was performed in 32 healthy non-atopic, non-smoking volunteers (16 women aged 26–63 years (mean 44) and 16 men aged 23–63 years (mean 39)). Cytospin preparations for differential counts of BAL fluid cells and surface antigen expression of lymphocytes from BAL fluid and blood were analysed by flow cytometry.RESULTSMost parameters in the BAL fluid changed with age in women. The percentage of CD4+ lymphocytes increased with age from a mean of 48 (SD10)% in women aged ⩽40 years to 69 (11)% in women aged >43 years (p=0.001). The percentage of CD8+ lymphocytes tended to decrease with age and the CD4/CD8 ratio was 5.8 (1.2) in women aged >43 years compared with 2.1 (0.7) in those aged ⩽40 years (p<0.0001). Women aged >43 years differed from men aged >43 years as well as from younger subjects of both sexes with respect to CD4+ cells and CD4/CD8 ratio, and from younger women with respect to CD8+ cells. There was no age related change in the CD4/CD8 ratio in blood. No sex related differences were seen in the blood or BAL fluid of adults below the age of 40 years.CONCLUSIONSThe composition of lymphocytes with different phenotypes in the lower respiratory tract changes with age in women but not in men. This may have implications for some clinical conditions such as chronic dry cough which are observed predominantly in women.


1997 ◽  
Vol 107 (3) ◽  
pp. 593-600 ◽  
Author(s):  
F. BARRAT ◽  
B. M. LESOURD ◽  
A. LOUISE ◽  
H.-J. BOULOUIS ◽  
S. VINCENT-NAULLEAU ◽  
...  

Lung Cancer ◽  
2000 ◽  
Vol 30 (3) ◽  
pp. 169-174 ◽  
Author(s):  
Tokujiro Yano ◽  
Kenji Sugio ◽  
Koji Yamazaki ◽  
Shinichiro Kase ◽  
Masafumi Yamaguchi ◽  
...  

2002 ◽  
Vol 45 (1) ◽  
pp. 155-167 ◽  
Author(s):  
Aleida Vazquez-Macias ◽  
Perla Martinez-Cruz ◽  
Maria Cristina Castaneda-Patlan ◽  
Christine Scheidig ◽  
Jurg Gysin ◽  
...  

2007 ◽  
Vol 75 (9) ◽  
pp. 4272-4281 ◽  
Author(s):  
Qilong Xu ◽  
Sunita V. Seemanaplli ◽  
Kristy McShan ◽  
Fang Ting Liang

ABSTRACT Tight regulation of surface antigenic expression is crucial for the pathogenic strategy of the Lyme disease spirochete, Borrelia burgdorferi. Here, we report the influence of increasing expression of decorin-binding protein A (DbpA), one of the most investigated spirochetal surface adhesins, on the 50% infectious dose (ID50), dissemination, tissue colonization, pathogenicity, and persistence of B. burgdorferi in the murine host. Our in vitro assays showed that increasing DbpA expression dramatically increased the interaction of B. burgdorferi with decorin and sensitivity to growth inhibition/killing by anti-DbpA antibodies; however, this increased interaction did not affect spirochetal growth and replication in the presence of decorin. Increasing DbpA expression significantly reduced ID50 values and severely impaired dissemination in severe combined immunodeficiency (SCID) and immunocompetent mice. During infection of SCID mice, B. burgdorferi with increased DbpA expression was able to effectively colonize heart and skin tissues, but not joint tissues, completely abrogating arthritis virulence. Although increasing DbpA expression did not affect spirochetal persistence in the skin, it diminished the ability of B. burgdorferi to persist in the heart and joint tissues during chronic infection of immunocompetent mice. Taken together, the study highlights the importance of controlling surface antigen expression in the infectivity, dissemination, tissue colonization, pathogenicity, and persistence of B. burgdorferi during mammalian infection.


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