Cytokine profiles and phenotype regulation of antigen presenting cells by genotype-I porcine reproductive and respiratory syndrome virus isolates
Veterinary Research
Cytokine profiles and phenotype regulation of antigen presenting cells by genotype-I porcine reproductive and respiratory syndrome virus isolates
Mariona Gimeno 0 2 3
Laila Darwich 0 2 3
Ivan Diaz 2
Eugenia de la Torre 2
Joan Pujols 2
Marga Martn 0 2 3
Shigeki Inumaru 1
Esmeralda Cano 2
Mariano Domingo 0 2 3
Maria Montoya 2
Enric Mateu 0 2 3
0 Departament de Sanitat i d'Anatomia Animals, Facultat de Veterinaria, Universitat Autonoma de Barcelona , 08193 Cerdanyola del Valles , Spain
1 NARO National Institute of Animal Health , Kannondai, Tsukuba, Ibaraki , Japan
2 Centre de Recerca en Sanitat Animal (CReSA) , UAB-IRTA, campus UAB, Edifici CR, 08193 Cerdanyola del Valles , Spain
3 Departament de Sanitat i d'Anatomia Animals, Facultat de Veterinaria, Universitat Autonoma de Barcelona , 08193 Cerdanyola del Valles , Spain
The present study examined the immunological response of antigen presenting cells (APC) to genotype-I isolates of porcine reproductive and respiratory syndrome virus (PRRSV) infection by analysing the cytokine profile induced and evaluating the changes taking place upon infection on immunologically relevant cell markers (MHCI, MHCII, CD80/86, CD14, CD16, CD163, CD172a, SWC9). Several types of APC were infected with 39 PRRSV isolates. The results show that different isolates were able to induce different patterns of IL-10 and TNF-a. The four possible phenotypes based on the ability to induce IL-10 and/or TNF-a were observed, although different cell types seemed to have different capabilities. In addition, isolates inducing different cytokine-release profiles on APC could induce different expression of cell markers.
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Introduction
Porcine reproductive and respiratory syndrome virus
(PRRSV) is one of the major pathogens affecting the
swine industry worldwide. Control of the infection has
proven to be difficult because of the limited knowledge
on the ways by which the virus is transmitted between
herds and also because of the lack of fully and
universally protective vaccines. One of the main obstacles for
the development of efficacious vaccines against PRRSV
is the very partial understanding of PRRS
immunopathogenesis. A few years ago, several papers
comprehensively described the adaptive immune response to
PRRS and showed that after infection or vaccination
with either European or American PRRSV strains, pigs
develop a rapid humoral response devoid of neutralising
antibodies (NA). For some not yet fully elucidated
reasons, NA develop much later in the course of infection
[1]. Cell-mediated immunity, measured as virus-specific
interferon-gamma (IFN-g) secreting cells (SC), has an
erratic behaviour for several weeks after the onset of
infection [2-4] showing afterwards a trend to increase
and reach a steady state. To explain such a unique
picture of the adaptive immune response against viral
infection seems to rely mostly but not only, on the early
events of the innate immune response [5,6].
Early studies [7] showed that PRRSV was unable to
induce significant IFN-a responses in vivo or in vitro.
Also, infection of porcine macrophages with PRRSV
impaired or abolished the IFN-a responses against
transmissible gastroenteritis virus that is known to be a potent
IFN-a inducer. Later on, other authors [8] showed that
different North American PRRSV (genotype-II) isolates
differed in their sensitivity to IFN-a and in their
capabilities for inducing this cytokine. These authors suggested
that the inhibition of IFN-a responses by PRRSV may be
mediated by post-transcriptional mechanisms of
regulation. IFN-a is not the only cytokine that seems to be
affected by PRRSV infection. Several papers showed that
interleukin-10 (IL-10) may play a role in the regulation of
the immune response in PRRSV infection both in vitro
and ex vivo [1-3,9,10]. Nevertheless, it has also been
reported that different strains may induce different IL-10
responses in PBMC [3] and, therefore, different outcomes
of the infection and the resulting immune response could
be expected after infection with different strains. In
addition, American-type PRRSV isolates seem to be able to
downregulate other important components of the early
immune response of antigen presenting cells (APC), in
particular major histocompatibility complex (MHC)
expression [10,11] and CD80/86 [12].
Taking into account those previous reports, it has
become evident that IFN-a and IL-10 are clear targets
for studying the regulation of the immune response
against PRRSV. However, the available evidences suggest
that different strains may probably produce different
cytokine release patterns [13].
In the present study, a large collection of PRRSV
strains was chosen to study the in vitro effects of
PRRSV in different types of APC, with particular
emphasis on cytokine profiles and the regulation of
immunologically relevant cell markers. The participation
of APC in the immune response is crucial and the
examination of cytokine responses may provide
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