PMID- 24293628
OWN - NLM
STAT- MEDLINE
DCOM- 20140227
LR  - 20211021
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 192
IP  - 1
DP  - 2014 Jan 1
TI  - MyD88 signaling regulates both host defense and immunopathogenesis during 
      pneumocystis infection.
PG  - 282-92
LID - 10.4049/jimmunol.1301431 [doi]
AB  - The immune response protects against Pneumocystis infection but is also a key 
      component of Pneumocystis pneumonia (PcP)-related immunopathogenesis. Signaling 
      through myeloid differentiation factor 88 (MyD88) is critical for activation of 
      immune pathways downstream of TLRs and IL-1R. To determine whether MyD88 
      regulates normal host defense against Pneumocystis, nonimmunosuppressed wild-type 
      (WT) and MyD88-deficient mice were infected. MyD88(-/-) mice had higher early 
      Pneumocystis burdens than did WT mice but mounted an effective adaptive immune 
      response and cleared Pneumocystis similarly to WT. However, MyD88(-/-) mice 
      displayed a more intense and prolonged pulmonary immune response than did WT 
      mice. To determine the role of MyD88 in the development of PcP-related 
      immunopathogenesis, WT and MyD88(-/-) mice were rendered susceptible to PcP by 
      depletion of CD4(+) T cells. At 4 wk postinfection, CD4-depleted WT and 
      MyD88(-/-) mice harbored similar organism burdens, but MyD88(-/-) mice were 
      protected from the PcP-related respiratory impairment observed in WT mice. 
      Improved pulmonary physiology in MyD88(-/-) mice correlated with lower lung CCL2 
      levels and reduced cell recruitment. However, by 5 wk postinfection, the overall 
      health of MyD88(-/-) mice began to deteriorate rapidly relative to WT, with 
      accelerated weight loss, impaired lung function, and exacerbated alveolar 
      inflammation. This physiological decline of MyD88(-/-) mice was associated with 
      increased TNF-alpha and IFN-gamma in the lung, and by the inability to control 
      Pneumocystis burden. Thus, MyD88 is not required for resistance to Pneumocystis 
      infection, but limits the adaptive immune response in immunocompetent mice. In 
      the setting of active PcP, MyD88 signaling contributes to both immunopathogenesis 
      and control of fungal burden.
FAU - Bello-Irizarry, Sheila N
AU  - Bello-Irizarry SN
AD  - Department of Microbiology and Immunology, University of Rochester School of 
      Medicine and Dentistry, Rochester, NY 14642.
FAU - Wang, Jing
AU  - Wang J
FAU - Johnston, Carl J
AU  - Johnston CJ
FAU - Gigliotti, Francis
AU  - Gigliotti F
FAU - Wright, Terry W
AU  - Wright TW
LA  - eng
GR  - R01 HL113495/HL/NHLBI NIH HHS/United States
GR  - HL113495/HL/NHLBI NIH HHS/United States
GR  - T32 AR053459/AR/NIAMS NIH HHS/United States
GR  - R01 HL083761/HL/NHLBI NIH HHS/United States
GR  - HL083761/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20131129
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Chemokines)
RN  - 0 (Cytokines)
RN  - 0 (Myeloid Differentiation Factor 88)
SB  - IM
MH  - Animals
MH  - Bone Marrow Cells/metabolism
MH  - Chemokines/biosynthesis
MH  - Colony Count, Microbial
MH  - Cytokines/biosynthesis
MH  - Female
MH  - Hematopoiesis/genetics
MH  - Lung/immunology/microbiology/pathology
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Myeloid Differentiation Factor 88/deficiency/genetics/*metabolism
MH  - Pneumocystis/*immunology
MH  - Pneumocystis Infections/genetics/*immunology/*metabolism/microbiology
MH  - *Signal Transduction
PMC - PMC4140532
MID - NIHMS535102
EDAT- 2013/12/03 06:00
MHDA- 2014/02/28 06:00
PMCR- 2015/01/01
CRDT- 2013/12/03 06:00
PHST- 2013/12/03 06:00 [entrez]
PHST- 2013/12/03 06:00 [pubmed]
PHST- 2014/02/28 06:00 [medline]
PHST- 2015/01/01 00:00 [pmc-release]
AID - jimmunol.1301431 [pii]
AID - 10.4049/jimmunol.1301431 [doi]
PST - ppublish
SO  - J Immunol. 2014 Jan 1;192(1):282-92. doi: 10.4049/jimmunol.1301431. Epub 2013 Nov 
      29.