The Journal of Immunology, 2001, 167: 11-14.
Copyright © 2001 by The American Association of Immunologists
Cutting Edge: Antibody-Mediated Cessation of Hemotropic Infection by the Intraerythrocytic Mouse Pathogen Bartonella grahamii1
Jan Koesling*,
Toni Aebischer*,
Christine Falch
,
Ralf Schülein,
and
Christoph Dehio2,,
*
Department of Molecular Biology, Max Planck Institute for Infection Biology, Berlin, Germany;
Department of Infection Biology, Max Planck Institute for Biology, Tubingen, Germany; and
Department of Molecular Microbiology, Biozentrum of the University of Basel, Basel, Switzerland
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Abstract
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The genus Bartonella includes important
human-specific and zoonotic pathogens which cause intraerythrocytic
bacteremia in their mammalian reservoir host(s). It is accepted that
cellular immunity plays a decisive role in the host’s defense against
most intracellular bacteria. Bartonella
sp. infection in the immunocompetent host typically
leads to immunity against homologous challenge. The basis of this
immunity, be it cellular or humoral, is unclear. In this study, the
course of Bartonella grahamii bacteremia in
immunocompetent and immunocompromised mice was compared. In
immunocompetent hosts, the bacteremia is transient and induces a strong
humoral immune response. In contrast, bacteremia persists in
immunocompromised B and T cell-deficient mice. Immune serum transfer
beginning with day 6 postinfection to B cell-deficient mice unable to
produce Igs converted the persistent bacteremia to a transient course
indistinguishable from that of immunocompetent animals. These data
demonstrate an essential role for specific Abs in abrogating the
intraerythrocytic bacteremia of B. grahamii in
mice.
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Introduction
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Two
Bartonella species, Bartonella bacilliformis and
Bartonella quintana, cause hemotropic infection in humans
known as oroya fever (1) and trench fever
(2), respectively. In the last decade, a number of
Bartonella spp. naturally causing hemotropic infection in
various mammals (i.e., cats, dogs, rats, and mice) have been associated
with an expanding spectrum of human diseases (3, 4, 5). The
intraerythrocytic lifestyle appears to be the common parasitic strategy
of all Bartonella spp. in their respective mammalian
reservoirs. The process of erythrocyte parasitism by
Bartonella has been studied in most detail in rats
experimentally infected by Bartonella tribocorum
(6). After residing in an unknown primary niche, the onset
of bacteremia in this model occurs 5–6 days postinfection by a
synchronous wave of bacterial adhesion and invasion into mature
erythrocytes. The intracellular bacteria replicate until reaching a
steady number, which is sustained for the remaining life span of the
infected erythrocytes (eventually exceeding several weeks). The initial
wave of erythrocyte infection is followed by reinfection waves
occurring in intervals of 3–6 days. As found similarly in other animal
models of Bartonella infection (7, 8, 9, 10), the
phase of intraerythrocytic bacteremia subsides spontaneously
after a few months (typically 8–10 wk). The infection triggers an
immune response which confers protective immunity as challenging
convalescent animals with the same Bartonella strain does
not result in reinfection (7, 10), whereas challenging
with a different Bartonella strain may again cause
bacteremia (10). However, the immune effector mechanism(s)
mediating termination of Bartonella bacteremia are not yet
elucidated. Both a humoral immune response with high IgG titers
(10) as well as a cellular immune response by T cell
activation (8, 11, 12, 13) can be triggered by
Bartonella infection. Classical studies of intracellular
pathogens such as Listeria monocytogenes and
Mycobacterium tuberculosis have provided evidence for a
critical role for cellular immunity in host defense (14, 15). Therefore, cellular immune responses have long been
considered to be a hallmark of immunity to intracellular bacterial
pathogens (16). However, erythrocytes cannot present Ags
to the immune system in a MHC-dependent way due to the lack of MHC on
their surface. Intraerythrocytic bartonellae should thus be hidden from
a respective cellular immune response. A growing body of evidence
suggests that Ab can contribute to immunity against several other
intracellular pathogens (reviewed in Ref. 17), such as
Salmonella (18, 19), Mycobacterium
(20), Legionella (21),
Brucella (22), and Plasmodium
(23). A better understanding of the host immune
response(s) interfering with Bartonella infections may
facilitate the design of strategies to control these emerging
pathogens. To this end, we have established a mouse model of transient
Bartonella bacteremia in wild-type and persistent bacteremia
in B cell-deficient strains. Further by immune serum transfer we
formally demonstrate that Abs are required for immune control of
intraerythrocytic Bartonella infection in mice.
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Materials and Methods
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Mice, bacteria, and infection
Six- to 8-wk-old female BALB/c mice were purchased from Harlan
and Winkelmann (Borchen, Germany), C57BL/6 from Bundesinstitut
für gesundheitlichen Verbraucherschutz und
Veterinärmedizin (Berlin, Germany),
C57BL/6-Igh-/-
(Igh-/-) and
C57BL/6-Rag1-/- (Rag-/-) mice
from The Jackson Laboratory (Bar Harbor, ME). A Bartonella
isolate from field-vole (strain IBS 376, generously provided by Yves
Piémont, Strasbourg, France) was identified as B.
grahamii by sequence analysis of the citrate synthase
gene (gltA) as previously described (24).
Bacteria were cultivated on Columbia blood agar with 5%
defibrinated sheep blood (CB-agar)3 at 35°C and 5%
CO2 for 7 days, and 2 x
109 CFU suspended in 200 µl PBS were injected
i.v. Bacteremia was analyzed by plating citrate blood samples
previously frozen at -80°C on CB-agar and CFU enumeration.
Serum transfer experiments
Serum was obtained from blood pooled from 20 C57BL/6 mice.
Normal serum was collected from naive mice and immune serum from mice
40–82 days postinfection. To increase the Ig concentration, serum
precipitation was performed with 45% ammonium sulfate
(25). The precipitate was dialyzed against PBS. On days 6,
11, 18, and 32 postinfection, 1 mg protein of normal or immune serum
precipitate within 300 µl PBS or PBS alone was injected i.v. into
B. grahamii-infected mice.
ELISA
Ab titers were determined colorimetrically by solid-phase ELISA
essentially as described (26), except that B.
grahamii whole cell lysate was used for Ag coating of microtiter
plates. In brief, dilutions of serum samples were added into Ag-coated
microtiter plates. For detection, HRP-conjugated rat anti-mouse
IgG1 or IgG2a (Nordic, Tilburg, The Netherlands) and
orthophenyldiamine-supplemented peroxide were used. Absorbance was
measured at 492 nm.
Intraeythrocytic bacteria
The gentamicin protection assay was performed as described
previously (6). Blood smears were stained by SpotTest
acridine orange stain as specified by the manufacturer (Difco, Detroit,
MI) and fluorescent intraerythrocytic bacteria were visualized by a
Leica DM IRBE inverted fluorescence microscope (Leica, Deerfield, IL)
using filter block GFP.
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Results and Discussion
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B. grahamii has been isolated from the blood of various
small woodland mammals including wild mice (27, 28). To
establish a murine infection model for immunological studies, we
injected B. grahamii i.v. into wild-type C57BL/6 or BALB/c
mice and determined the course of bacteremia by CFU enumeration. The
course of B. grahamii bacteremia was indistinguishable for
both mouse strains and is illustrated for C57BL/6 in Fig. 1
A (data for BALB/c not
shown). All four inoculated animals were bacteremic by 1 wk
postinfection, and bacteremia peaked at 2 wk before dropping below
detectable levels between 8 and 11 wk postinfection. The observed
characteristics of B. grahamii bacteremia in experimentally
infected wild-type mice are consistent with the well-characterized
B. tribocorum rat model (6) as well as other
animal models of Bartonella infection
(7, 8, 9, 10).
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FIGURE 1. B. grahamii infection of mice and their humoral immune
response. Infection of immunocompetent C57BL/6 mice
(n = 4) was performed by i.v. injection of 2
x 109 CFU suspended in 200 µl PBS. Serum and citrate
blood samples were collected on days 5, 10, 17, 31, 45, 59, and 77
postinfection. A, Time course of the bacteremia. CFU per
ml of citrate blood were determined by culture on CB-agar plates
performed in triplicates. Averages were plotted for individual animals
(C57BL/6 #1–4). B, IgG1 and IgG2a Abs in pooled serum
of infected C57BL/6 mice (n = 4) at day 45
postinfection. Titers were determined by serial dilution in an ELISA of
B. grahamii whole-cell lysates, and the averages of the
chromogenic readout (A492) performed in
triplicates were plotted. The plot illustrates the linear range of the
test (>1:30 for IgG1 and 1:1,000–1:10,000 for IgG2a).
C, Time course of the IgG response. Individual serum
samples diluted within the linear test range (1:15 for IgG1 and 1:2,000
for IgG2a) were examined by ELISA. For each time point, averages of the
chromogenic readout (OD492) performed in triplicates for
all four animals (C57BL/6 #1–4) were plotted and SDs are indicated as
bars.
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The intracellular localization of B. grahamii was confirmed
by gentamicin protection assays (6), which permit the
distinction between extracellular and intracellular bacteria.
Furthermore, fluorescence microscopic examination of acridine
orange-stained blood smears indicated an intraerythrocytic localization
of bacteria (data not shown).
The humoral response triggered by B. grahamii infection in
C57BL/6 was measured by a solid-phase ELISA. IgG1 and IgG2a titers
(Fig. 1
B) were determined by serial dilution of serum from
day 45 postinfection. Appropriate dilutions of all serum samples
were prepared (1:15 for IgG1 and 1:2000 for IgG2a) to measure the
time course of Ab titers in the linear range of the ELISA (Fig. 1C). These data clearly demonstrate that B.
grahamii infection of wild-type C57BL/6 mice triggers a strong Ab
response dominated by high relative titers of IgG2a compared with a
moderate IgG1 response (Fig. 1C).
To evaluate the specific Igs produced by B cells and eventually an
additional contribution of T cells for abrogating infection, the
bacteremic course in infected immunocompetent C57BL/6 mice was compared
with that in congenic immunocompromised animals. In
Igh-/- mice lacking Ig-producing B cells and in
Rag-/- mice devoid of both an intact B and T
cell compartment, the hemotropic infection increased for at least 4 wk
and persisted at a steady level (Fig. 2).
These data clearly demonstrate that B cells or Abs were necessary to
abrogate an infection of B. grahamii. The additional absence
of T cells in Rag-/-mice did not result in
higher CFUs/ml blood than in Igh-/- mice.
Interestingly, the persistent bacteremia in both immunodeficient mouse
strains is not fatal, indicating a high degree of adaptation of
B. grahamii to cause long-lasting infections in its
reservoir host organism.
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FIGURE 2. Course of B. grahamii bacteremia in immunodeficient (T
and/or B cell-deficient) mice.
C57BL/6-Rag1-/-
(n = 5),
C57BL/6-Igh-/-
(n = 5), and C57BL/6 wild type
(n = 4) were B. grahamii infected by
i.v. injection of 2 x 109 CFU/200 µl PBS. Citrate
blood samples were collected on days 5, 10, 17, 31, 45, 59, and 77
postinfection. CFU per milliliter of citrate blood were determined by
culture on CB-agar plates performed in triplicates. Average values were
plotted and SDs indicated as bars.
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To evaluate the role of Abs specific for B. grahamii to
control bacteremia, we adoptively transferred serum Igs to infected
recipients. Igs from serum pools from naive (normal serum) or B.
grahamii infected C57BL/6 mice (immune serum) were precipitated by
ammonium sulfate and dialyzed against PBS. Ig obtained from immune
serum contained relatively high titers of IgG2a and moderate titers for
IgG1 directed against B. grahamii Ags (Fig. 3A). This composition agreed
with the relative titers of IgG isotypes in sera from infected mice
(Fig. 1B). On days 6, 11, 18, and 32 postinfection, Igs were
injected i.v. into infected immunodeficient recipients. The success of
the transfer of specific Abs was confirmed by determining
anti-B. grahamii IgG titers in serum from the recipient
mice (data not shown). Fig. 3B illustrates that transfer of
the PBS carrier or Ig from normal serum had no measurable effect on the
persistence of bacteremia in Igh-/- mice. In
contrast, transfer of immune serum Ig resulted in a transient
bacteremia indistinguishable from the course of Bartonella
bacteremia observed in immunocompetent C57BL/6 mice (cf Fig. 2). These
data conclusively demonstrate an essential role for Abs in terminating
the B. grahamii infection in mice.
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FIGURE 3. Effect of serum transfer on B. grahamii infection of
C57BL/6-Igh-/- (B cell-deficient)
mice. A, IgG1 and IgG2a titers in serum precipitates.
Serum pooled from 20 naive or B. grahamii-infected
C57BL/6 mice were precipitated, dialyzed, and adjusted to 1 mg
protein/300 µl PBS. B. grahamii-reactive
immunoglobulins within serial dilutions of serum precipitates were
determined by ELISA and the average values of the chromogenic readout
(OD492) performed in triplicates were plotted.
B, Time course of the bacteremia.
C57BL/6-Igh-/- mice
(n = 5) were infected with B.
grahamii followed on days 6, 11, 18, and 32 postinfection by
i.v. injection of either PBS or 1-mg protein doses of normal or
infected serum precipitate. Citrate blood samples were collected on
days 5, 10, 17, 31, 45, 59, and 77 postinfection. CFU per mililiter of
citrate blood were determined by culture on CB-agar plates performed in
triplicates. Average values were plotted and SDs are indicated as
bars.
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There appear to be multiple mechanisms by which Ab can influence
the course of infections with intracellular pathogens
(17). For example, specific Abs bind to
Plasmodium spp. Ag exposed on the surface of infected
erythrocytes (29). Such binding may cause
complement-mediated host cell lysis and opsonization. Opsonized
erythrocytes are more prone to macrophage phagocytosis
(30). If a similar mechanism would operate against
Bartonella-infected erythrocytes, infections should be
rapidly cleared after immune serum transfer. Instead, we favor the idea
that Ab mediate killing of extracellular Bartonella or
prevent their invasion into erythrocytes. We have shown that in rats
invasion of erythrocytes occurs in periodical waves every 3–6
days, seeded from a yet uncharacterized primary niche (6).
If these reinfection waves are terminated by neutralizing Ab, the
intraerythrocytic bacteremia should remain until the infected, aging
erythrocyte population is cleared. Since the infection of erythrocytes
by bartonellae is typically nonhemolytic (except for B.
bacilliformis in humans) and persists the life span of this
terminally differentiated cell type (6), the course of the
hemotropic Bartonella infection should reflect the average
lifetime of erythrocytes. The characteristic prolonged course of
bacteremia in immunocompetent mice or Igh-/-
mice after immune serum transfer is indeed consistent with this
idea.
In summary, we have established a mouse model for transient and
persistent B. grahamii infection. By immune serum transfer
to infected immunocompromised mice, we provide convincing evidence that
a specific Ab response is required to abrogate the intraerythrocytic
bacteremia. For the design of vaccination strategies against zoonotic
Bartonella in their mammalian reservoirs, this model should
allow testing if transferred Abs alone can provide immunity to primary
challenge infection and may aid identifying Ags that elicit
neutralizing Ab.
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Acknowledgments
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We thank Dr. Yves Piémont (University Louis Pasteur,
Strasbourg, France) for providing bacterial strains. We are grateful to
Robert Hurwitz and Annette Dietrich for their excellent technical
assistance. We also thank Christopher Snyder for critically reading
this manuscript. We thank Dr. Thomas F. Meyer for his interest and
continuous support.
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Footnotes
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1 This work was supported by Deutsche Forschungsgemeinschaft Grant De 539/4-1 and Swiss National Science Foundation Grant 3100-061777.00/1 (both to C.D.). 
2 Address correspondence and reprint requests to Dr. Christoph Dehio, Department of Molecular Microbiology, Biozentrum of the University of Basel, Klingelbergstrasse 70, CH-4056 Basel, Switzerland. E-mail address: christoph.dehio{at}unibas.ch
3 Abbreviation used in this paper: CB-agar, Columbia blood agar with 5% defibrinated sheep blood.
Received for publication February 7, 2001.
Accepted for publication May 7, 2001.
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References
|
|---|
-
Raynafarje, C., J. Ramos. 1961. The hemolytic anemia of human bartonellosis. Blood 17:562.[Abstract/Free Full Text]
-
Bass, J. W., J. M. Vincent, D. A. Person. 1997. The expanding spectrum of Bartonella infections: I. Bartonellosis and trench fever. Pediatr. Infect. Dis. J. 16:2.[Medline]
-
Bass, J. W., J. M. Vincent, D. A. Person. 1997. The expanding spectrum of Bartonella infections: II. Cat-scratch disease. Pediatr. Infect. Dis. J. 16:163.[Medline]
-
Kerkhoff, F. T., A. M. Bergmans, A. van Der Zee, A. Rothova. 1999. Demonstration of Bartonella grahamii DNA in ocular fluids of a patient with neuroretinitis. J. Clin. Microbiol. 37:4034.[Abstract/Free Full Text]
-
Dehio, C., A. Sander. 1999. Bartonella as emerging pathogens. Trends Microbiol. 7:226.[Medline]
-
Schulein, R., A. Seubert, C. Gille, C. Lanz, Y. Hansmann, Y. Piemont, C. Dehio. 2001. Invasion and persistent intracellular colonization of erythrocytes: a unique parasitic strategy of the emerging pathogen. Bartonella. J. Exp. Med. 193:1077.
-
Regnery, R. L., J. A. Rooney, A. M. Johnson, S. L. Nesby, P. Manzewitsch, K. Beaver, J. G. Olson. 1996. Experimentally induced Bartonella henselae infections followed by challenge exposure and antimicrobial therapy in cats. [Published erratum appears in 1997 Am. J. Vet. Res., 58:803.]. Am. J. Vet. Res. 57:1714.[Medline]
-
Guptill, L., L. Slater, C. C. Wu, T. L. Lin, L. T. Glickman, D. F. Welch, H. HogenEsch. 1997. Experimental infection of young specific pathogen-free cats with Bartonella henselae. J. Infect. Dis. 176:206.[Medline]
-
Guptill, L., L. Slater, C. C. Wu, L. T. Glickman, T. L. Lin, D. F. Welch, J. T. Crippen, H. HogenEsch. 1999. Immune response of neonatal specific pathogen-free cats to experimental infection with Bartonella henselae. Vet. Immunol. Immunopathol. 71:233.[Medline]
-
Kosoy, M. Y., R. L. Regnery, O. I. Kosaya, J. E. Childs. 1999. Experimental infection of cotton rats with three naturally occurring Bartonella species. J. Wildl. Dis. 35:275.[Abstract]
-
Arvand, M., M. E. Mielke, K. Sterry, H. Hahn. 1998. Detection of specific cellular immune response to Bartonella henselae in a patient with cat scratch disease. Clin. Infect. Dis. 27:1533.[Medline]
-
Karem, K. L., K. A. Dubois, S. L. McGill, R. L. Regnery. 1999. Characterization of Bartonella henselae-specific immunity in BALB/c mice. Immunology 97:352.[Medline]
-
Pappalardo, B. L., T. Brown, D. Gebhardt, S. Sontakke, E. B. Breitschwerdt. 2000. Cyclic CD8+ lymphopenia in dogs experimentally infected with Bartonella vinsonii subsp. berkhoffii. Vet Immunol Immunopathol 75:43.[Medline]
-
Miki, K., G. B. Mackaness. 1964. The passive transfer of acquired resistance to Listeria monocytogenes. J. Exp. Med. 120:93.[Abstract]
-
Lane, F. C., E. R. Unanue. 1972. Requirement of thymus (T) lymphocytes for resistance to listeriosis. J. Exp. Med. 135:1104.[Abstract]
-
Schaible, U. E., H. L. Collins, S. H. Kaufmann. 1999. Confrontation between intracellular bacteria and the immune system. Adv. Immunol. 71:267.[Medline]
-
Casadevall, A.. 1998. Antibody-mediated protection against intracellular pathogens. Trends Microbiol. 6:102.[Medline]
-
Eisenstein, T. K., L. M. Killar, B. M. Sultzer. 1984. Immunity to infection with Salmonella typhimurium: mouse-strain differences in vaccine- and serum-mediated protection. J. Infect. Dis. 150:425.[Medline]
-
Mittrucker, H. W., B. Raupach, A. Kohler, S. H. Kaufmann. 2000. Cutting edge: role of B lymphocytes in protective immunity against Salmonella typhimurium infection. J. Immunol. 164:1648.[Abstract/Free Full Text]
-
Teitelbaum, R., A. Glatman-Freedman, B. Chen, J. B. Robbins, E. Unanue, A. Casadevall, B. R. Bloom. 1998. A mAb recognizing a surface antigen of Mycobacterium tuberculosis enhances host survival. Proc. Natl. Acad. Sci. USA 95:15688.[Abstract/Free Full Text]
-
Brieland, J. K., L. A. Heath, G. B. Huffnagle, D. G. Remick, M. S. McClain, M. C. Hurley, R. K. Kunkel, J. C. Fantone, C. Engleberg. 1996. Humoral immunity and regulation of intrapulmonary growth of Legionella pneumophila in the immunocompetent host. J. Immunol. 157:5002.[Abstract]
-
Cloeckaert, A., I. Jacques, P. de Wergifosse, G. Dubray, J. N. Limet. 1992. Protection against Brucella melitensis or Brucella abortus in mice with immunoglobulin G (IgG), IgA, and IgM monoclonal antibodies specific for a common epitope shared by the Brucella A and M smooth lipopolysaccharides. Infect. Immun. 60:312.[Abstract/Free Full Text]
-
Matsumoto, S., H. Yukitake, H. Kanbara, T. Yamada. 1999. Long-lasting protective immunity against rodent malaria parasite infection at the blood stage by recombinant BCG secreting merozoite surface protein-1. Vaccine 18:832.[Medline]
-
Birtles, R. J., D. Raoult. 1996. Comparison of partial citrate synthase gene (gltA) sequences for phylogenetic analysis of Bartonella species. Int. J. Syst. Bacteriol. 46:891.[Abstract/Free Full Text]
-
Dunbar, B. S., E. D. Schwoebel. 1990. Preparation of polyclonal antibodies. Methods Enzymol. 182:663.[Medline]
-
Gomez-Duarte, O. G., B. Lucas, Z. X. Yan, K. Panthel, R. Haas, T. F. Meyer. 1998. Protection of mice against gastric colonization by Helicobacter pylori by single oral dose immunization with attenuated Salmonella typhimurium producing urease subunits A and B. Vaccine 16:460.[Medline]
-
Birtles, R. J., T. G. Harrison, D. H. Molyneux. 1994. Grahamella in small woodland mammals in the U.K.: isolation, prevalence and host specificity. Ann. Trop. Med. Parasitol. 88:317.[Medline]
-
Birtles, R. J., T. G. Harrison, N. A. Saunders, D. H. Molyneux. 1995. Proposals to unify the genera Grahamella and Bartonella, with descriptions of Bartonella talpae comb. nov., Bartonella peromysci comb. nov., and three new species, Bartonella grahamii sp. nov., Bartonella taylorii sp. nov., and Bartonella doshiae sp. nov. Int. J. Syst. Bacteriol. 45:1.[Abstract/Free Full Text]
-
Choudhury, A., A. Goel, M. Raje, H. Vohra, G. C. Varshney. 1997. Recognition of the parasite infected cell surface determinants by homologous antiserum raised against infected cell membranes. Parasitol. Res. 83:746.[Medline]
-
Mota, M. M., K. N. Brown, A. A. Holder, W. Jarra. 1998. Acute Plasmodium chabaudi chabaudi malaria infection induces antibodies which bind to the surfaces of parasitized erythrocytes and promote their phagocytosis by macrophages in vitro. Infect. Immun. 66:4080.[Abstract/Free Full Text]
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Abstract
Introduction
