Abstract
BACKGROUND: Influenza virus infection during pregnancy is associated with enhanced disease severity. However, the underlying mechanisms are still not fully understood. We hypothesized that normal alveolar macrophage (AM) functions, which are central to maintaining lung immune homeostasis, are altered during pregnancy and that this dysregulation contributes to the increased inflammatory response to influenza virus infection. METHODS: Time-mated BALB/c mice were infected with a low dose of H1N1 influenza A virus at gestation day 9.5. Inflammatory cells in bronchoalveolar lavage (BAL) fluid were assessed by flow cytometry. RESULTS: Our findings confirm previous reports of increased severity of influenza virus infection in pregnant mice. The heightened inflammatory response detected in BAL fluid from infected pregnant mice was characterized by neutrophil-rich inflammation with concomitantly reduced numbers of AM, which were slower to return to baseline counts, compared with nonpregnant infected mice. The increased infection severity and inflammatory responses to influenza during pregnancy were associated with a pregnancy-induced shift in AM phenotype at homeostatic baseline, from the M1 (ie, classical activation) state toward the M2 (ie, alternative activation) state, as evidence by increased expression of CD301 and reduced levels of CCR7. CONCLUSION: These results show that pregnancy is associated with an alternatively activated phenotype of AM before infection, which may contribute to heightened disease severity.
| Original language | English |
|---|---|
| Pages (from-to) | 1823-1831 |
| Number of pages | 9 |
| Journal | The Journal of infectious diseases |
| Volume | 219 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - 5 May 2019 |
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Pregnancy Induces a Steady-State Shift in Alveolar Macrophage M1/M2 Phenotype That Is Associated With a Heightened Severity of Influenza Virus Infection : Mechanistic Insight Using Mouse Models. / Lauzon-Joset, Jean Francois; Scott, Naomi M.; Mincham, Kyle T.; Stumbles, Philip A.; Holt, Patrick G.; Strickland, Deborah H.
In: The Journal of infectious diseases, Vol. 219, No. 11, 05.05.2019, p. 1823-1831.Research output: Contribution to journal › Article
TY - JOUR
T1 - Pregnancy Induces a Steady-State Shift in Alveolar Macrophage M1/M2 Phenotype That Is Associated With a Heightened Severity of Influenza Virus Infection
T2 - Mechanistic Insight Using Mouse Models
AU - Lauzon-Joset, Jean Francois
AU - Scott, Naomi M.
AU - Mincham, Kyle T.
AU - Stumbles, Philip A.
AU - Holt, Patrick G.
AU - Strickland, Deborah H.
PY - 2019/5/5
Y1 - 2019/5/5
N2 - BACKGROUND: Influenza virus infection during pregnancy is associated with enhanced disease severity. However, the underlying mechanisms are still not fully understood. We hypothesized that normal alveolar macrophage (AM) functions, which are central to maintaining lung immune homeostasis, are altered during pregnancy and that this dysregulation contributes to the increased inflammatory response to influenza virus infection. METHODS: Time-mated BALB/c mice were infected with a low dose of H1N1 influenza A virus at gestation day 9.5. Inflammatory cells in bronchoalveolar lavage (BAL) fluid were assessed by flow cytometry. RESULTS: Our findings confirm previous reports of increased severity of influenza virus infection in pregnant mice. The heightened inflammatory response detected in BAL fluid from infected pregnant mice was characterized by neutrophil-rich inflammation with concomitantly reduced numbers of AM, which were slower to return to baseline counts, compared with nonpregnant infected mice. The increased infection severity and inflammatory responses to influenza during pregnancy were associated with a pregnancy-induced shift in AM phenotype at homeostatic baseline, from the M1 (ie, classical activation) state toward the M2 (ie, alternative activation) state, as evidence by increased expression of CD301 and reduced levels of CCR7. CONCLUSION: These results show that pregnancy is associated with an alternatively activated phenotype of AM before infection, which may contribute to heightened disease severity.
AB - BACKGROUND: Influenza virus infection during pregnancy is associated with enhanced disease severity. However, the underlying mechanisms are still not fully understood. We hypothesized that normal alveolar macrophage (AM) functions, which are central to maintaining lung immune homeostasis, are altered during pregnancy and that this dysregulation contributes to the increased inflammatory response to influenza virus infection. METHODS: Time-mated BALB/c mice were infected with a low dose of H1N1 influenza A virus at gestation day 9.5. Inflammatory cells in bronchoalveolar lavage (BAL) fluid were assessed by flow cytometry. RESULTS: Our findings confirm previous reports of increased severity of influenza virus infection in pregnant mice. The heightened inflammatory response detected in BAL fluid from infected pregnant mice was characterized by neutrophil-rich inflammation with concomitantly reduced numbers of AM, which were slower to return to baseline counts, compared with nonpregnant infected mice. The increased infection severity and inflammatory responses to influenza during pregnancy were associated with a pregnancy-induced shift in AM phenotype at homeostatic baseline, from the M1 (ie, classical activation) state toward the M2 (ie, alternative activation) state, as evidence by increased expression of CD301 and reduced levels of CCR7. CONCLUSION: These results show that pregnancy is associated with an alternatively activated phenotype of AM before infection, which may contribute to heightened disease severity.
KW - bronchoalveolar lavage
KW - flow cytometry
KW - Immunity
KW - M2 macrophage
KW - pregnant
KW - virus
UR - http://www.scopus.com/inward/record.url?scp=85065635762&partnerID=8YFLogxK
U2 - 10.1093/infdis/jiy732
DO - 10.1093/infdis/jiy732
M3 - Article
VL - 219
SP - 1823
EP - 1831
JO - Journal Infectious Diseases
JF - Journal Infectious Diseases
SN - 0022-1899
IS - 11
ER -