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Review
. 2024 Feb 27;4(3):326-340.
doi: 10.1016/j.jointm.2024.01.001. eCollection 2024 Jul.

Compartmentalization of the inflammatory response during bacterial sepsis and severe COVID-19

Jean-Marc Cavaillon  1 , Benjamin G Chousterman  2   3 , Tomasz Skirecki  4
Affiliations
Review

Compartmentalization of the inflammatory response during bacterial sepsis and severe COVID-19

Jean-Marc Cavaillon et al. J Intensive Med. .

Abstract

Acute infections cause local and systemic disorders which can lead in the most severe forms to multi-organ failure and eventually to death. The host response to infection encompasses a large spectrum of reactions with a concomitant activation of the so-called inflammatory response aimed at fighting the infectious agent and removing damaged tissues or cells, and the anti-inflammatory response aimed at controlling inflammation and initiating the healing process. Fine-tuning at the local and systemic levels is key to preventing local and remote injury due to immune system activation. Thus, during bacterial sepsis and Coronavirus disease 2019 (COVID-19), concomitant systemic and compartmentalized pro-inflammatory and compensatory anti-inflammatory responses are occurring. Immune cells (e.g., macrophages, neutrophils, natural killer cells, and T-lymphocytes), as well as endothelial cells, differ from one compartment to another and contribute to specific organ responses to sterile and microbial insult. Furthermore, tissue-specific microbiota influences the local and systemic response. A better understanding of the tissue-specific immune status, the organ immunity crosstalk, and the role of specific mediators during sepsis and COVID-19 can foster the development of more accurate biomarkers for better diagnosis and prognosis and help to define appropriate host-targeted treatments and vaccines in the context of precision medicine.

Keywords: Acute respiratory distress syndrome; Bone marrow; Cytokines; Lungs; Mucosa; Vaccines.

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Figures

Figure 1:
Figure 1
Compartmentalization. In contrast to the hematopoietic compartments (blood, spleen) where immune cells are essentially immunosuppressed, leukocytes within the other organs are rather activated. While a crosstalk perpetuates the inflammatory process, some tissues are more prone to propagate the systemic inflammation. This is particularly the case of the lungs and adipose tissue during severe acute respiratory syndrome coronavirus 2 infection or the gut during bacterial sepsis. The role of bone marrow and the emergency hematopoiesis appears ambiguous.
Figure 2:
Figure 2
Lung vs. systemic immune responses in COVID-19 and remote organ injury.
Fig. 3:
Figure 3
The bone marrow in sepsis. During systemic infection PAMPs and cytokines enter bone marrow where they are sensed by both stromal and hematopoietic cells (including mature cells as macrophages and stem and progenitor cells). Induction of G-CSF, IL-1, IL-3, IFN, and Notch boost proliferation and myeloid differentiation of HSCs. HSCs also egress from the bone marrow due to altered chemokine gradients and proteolytic milieu. Massive inflammation leads to the generation of myeloid-derived suppressor cells which contribute to immunocompromised systemic response. Bone marrow macrophages not only sense PAMPs but also can bind haptoglobin via CD163 which activates them and, in some patients, lead to features of MAS. Macrophage-derived cytokines also modulate hematopoiesis. Tissue-resident T cells and NK cells reside in the bone marrow and are not paralyzed in sepsis as their splenic counterparts. NK cells are the source of IFN which induces anti-inflammatory phenotype of emigrating monocytes.
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